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1. In Vitro Modelling of Oral Microbial Invasion in the Human Colon

Author: Lucie Etienne-Mesmin, Victoria Meslier, Ophélie Uriot, Elora Fournier, Charlotte Deschamps, Sylvain Denis, Aymeric David, Sarah Jegou, Christian Morabito, Benoit Quinquis, Florence Thirion, Florian Plaza Oñate, Emmanuelle Le Chatelier, S. Dusko Ehrlich, Stéphanie Blanquet-Diot, Mathieu Almeida, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), MetaGenoPolis (MGP (US 1367)), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Microbiology (medical), metagenomics, General Immunology and Microbiology, Ecology, gut microbiota, Physiology, [SDV]Life Sciences [q-bio], Cell Biology, oral microbiota, oral microbial invasion, M-ARCOL, Infectious Diseases, mucus, Genetics
Abstract: International audience; Recent advances in the human microbiome characterization have revealed significant oral microbial detection in stools of dysbiotic patients. However, little is known about the potential interactions of these invasive oral microorganisms with commensal intestinal microbiota and the host. In this proof-of-concept study, we proposed a new model of oral-to-gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen-and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Oral invasion of the intestinal microbiota was simulated by injection of enriched saliva in the in vitro colon model inoculated with a fecal sample from the same healthy adult donor. The mucosal compartment of M-ARCOL was able to retain the highest species richness levels over time, while species richness levels decreased in the luminal compartment. This study also showed that oral microorganisms preferably colonized the mucosal microenvironment, suggesting potential oral-to-intestinal mucosal competitions. This new model of oral-to-gut invasion can provide useful mechanistic insights into the role of oral microbiome in various disease processes. IMPORTANCE Here, we propose a new model of oral-to-gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen-and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Our study revealed the importance of integrating the mucus compartment, which retained higher microbial richness during fermentation, showed the preference of oral microbial invaders for the mucosal resources, and indicated potential oral-to-intestinal mucosal competitions. It also underlined promising opportunities to further understand mechanisms of oral invasion into the human gut microbiome, define microbe-microbe and mucus-microbe interactions in a compartmentalized fashion, and help to better characterize the potential of oral microbial invasion and their persistence in the gut.
Published: 2023

2. Four functional profiles for fibre and mucin metabolism in the human gut microbiome

Author: Simon Labarthe, Sandra Plancade, Sebastien Raguideau, Florian Plaza Onate, Emmanuelle Le Chatelier, Marion Leclerc, Béatrice Laroche, from patterns to models in computational biodiversity and biotechnology (PLEIADE), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Earlham Institute [Norwich], MetaGenoPolis (MGP (US 1367)), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pendulum Therapeutics [San Francisco], Dynamiques de populations multi-échelles pour des systèmes physiologiques (MUSCA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), and Labarthe, Simon
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Background With the emergence of metagenomic data, multiple links between the gut microbiome and the host health have been shown. Deciphering these complex interactions require evolved analysis methods focusing on the microbial ecosystem functions. Despite the fact that host or diet-derived fibres are the most abundant nutrients available in the gut, the presence of distinct functional traits regarding fibre and mucin hydrolysis, fermentation and hydrogenotrophic processes has never been investigated. Results After manually selecting 91 KEGG orthologies and 33 glycoside hydrolases further aggregated in 101 functional descriptors representative of fibre and mucin degradation pathways in the gut microbiome, we used non-negative matrix factorization to mine metagenomic datasets. Four distinct metabolic profiles were further identified on a training set of 1153 samples and thoroughly validated on a large database of 2571 unseen samples from 5 external metagenomic cohorts. Profiles 1 and 2 are the main contributors to the fibre-degradation-related metagenome: they present contrasted involvement in fibre degradation and sugar metabolism and are differentially linked to dysbiosis, metabolic disease and inflammation. Profile 1 takes over Profile 2 inhealthy samples, and unbalance of these profiles characterize dysbiotic samples. Furthermore, high fibre diet favours a healthy balance between Profiles 1 and Profile 2. Profile 3 takes over Profile 2 during Crohn’s disease, inducing functional reorientations towards unusual metabolism such as fucose and H2S degradation or propionate, acetone and butanediol production. Profile 4 gathers under-represented functions, like methanogenesis. Two taxonomic makes up of the profiles were investigated, using either the covariation of 203 prevalent genomes or metagenomic species, both providing consistent results in line with their functional characteristics. This taxonomic characterization showed that Profiles 1 and 2 were respectively mainly composed of bacteria from the phyla Bacteroidetes and Firmicutes while Profile 3 is representative of Proteobacteria and Profile 4 of methanogens.Conclusions Integrating anaerobic microbiology knowledge with statistical learning can narrow down the metagenomic analysis to investigate functional profiles. Applying this approach to fibre degradation in the gut ended with 4 distinct functional profiles that can be easily monitored as markers of diet, dysbiosis, inflammation and disease.
Published: 2023

3. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamineN-oxide with implications for heart and kidney disorders

Author: Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia, Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe-Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael, Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Pedro Coelho, Luis, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Zucker, Jean-Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad, Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, Dumas, Marc-Emmanuel, Imperial College London, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitätsklinikum Leipzig, European Molecular Biology Laboratory [Heidelberg] (EMBL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Paris-Saclay Food and Bioproduct Engineering (SayFood), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Procédés biotechnologiques au service de l'environnement (UR PROSE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Charles Viollette (ICV) - ULR 7394 (ICV), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Institut Supérieur d'Agriculture-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: ObjectivesThe host-microbiota co-metabolite trimethylamineN-oxide (TMAO) is linked to increased thrombotic and cardiovascular risks. Here we, sought to i) characterize which host variables contribute to fasting serum TMAO levels in real-life settings ii) identify potential actionable therapeutic means related to circulating TMAO.DesignWe applied “explainable” machine learning, univariate-, multivariate- and mediation analyses of fasting plasma TMAO concentration and a multitude of bioclinical phenotypes in 1,741 adult Europeans of the MetaCardis study. We expanded and validated our epidemiological findings in mechanistic studies in human renal fibroblasts and a murine model of kidney fibrosis following TMAO exposure.ResultsNext to age, kidney function was the primary variable predicting circulating TMAO in MetaCardis, with microbiota composition and diet playing minor, albeit significant roles. Mediation analysis revealed a causal relationship between TMAO and kidney function decline that strengthened at more severe stages of cardiometabolic disease. We corroborated our findings in preclinical models where TMAO exposure augmented conversion of human renal fibroblasts into myofibroblasts and increased kidney scarringin vivo. Mechanistically, TMAO aggravated kidney fibrosis due to ERK1/2 hyperactivation synergistically with TGF-β1 signaling. Consistent with our findings, patients receiving next-generation glucose-lowering drugs with reno-protective properties, had significantly lower circulating TMAO when compared to propensity-score matched control individuals.ConclusionAfter age, kidney function is the major determinant of fasting circulating TMAO in adults. Our findings of lower TMAO levels in individuals medicated with reno-protective anti-diabetic drugs suggests a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk that merits urgent investigation in human trials.Data availability statementRaw shotgun sequencing data that support the findings of this study have been deposited in the European Nucleotide Archive with accession codes PRJEB37249, PRJEB38742, PRJEB41311 and PRJEB46098. Serum NMR and urine NMR metabolome data have been uploaded to Metabolights with accession number MTBLS3429; serum GC-MS and isotopically quantified serum metabolites (UPLC–MS/MS) are available from MassIVE with accession numbers MSV000088042 and MSV000088043, respectively.
Published: 2022

4. Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial

Author: Isaac Barroso, Isabel M. Miranda, Davide Carvalho, Paula Freitas, Maria Manuel Silva, Paul Picq, Eva Lau, Adelino Barbosa, Flora Correia, Joël Doré, Edi Prifti, Karine Clément, Cidália Pina Vaz, Eugeni Belda, Manuel Ferreira-Magalhães, Universidade do Porto = University of Porto, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Instituto de Investigação e Inovação em Saúde (I3S), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Faculdade de Ciências da Nutrição e Alimentação, Faculdade de Medicina, Universidade do Porto, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), and Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU)
Subjects: 0301 basic medicine, medicine.medical_specialty, Weight loss, RC620-627, Roux-en-Y gastric bypass, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Gut flora, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Diabetes mellitus, Randomized controlled trial, law, Internal medicine, Internal Medicine, Medicine, Microbiome, Nutritional diseases. Deficiency diseases, 2. Zero hunger, biology, business.industry, Research, Health sciences, Medical and Health sciences, Ciências médicas e da saúde, nutritional and metabolic diseases, medicine.disease, biology.organism_classification, Obesity, 3. Good health, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Medical and Health sciences, Ciências da Saúde, Ciências médicas e da saúde, medicine.symptom, business
Abstract: Background Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30–35 kg/m2). Methods DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass—RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. Results Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p p p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. Conclusions This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. Trial registration: ISRCTN53984585
Published: 2021

5. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients

Author: Xavier Thomas, Lilia Boucinha, Christian Recher, Anne-Sophie Michallet, Sophie Ducastelle-Lepretre, Mauricette Michallet, Stéphanie Nguyen, Clément Rocher, Pierre Peterlin, Etienne Paubelle, Florent Malard, Suzanne Tavitian, Colombe Saillard, Marie-Virginie Larcher, Sarah Bertoli, Evelyne D'incan-Corda, Ollivier Legrand, Patrice Chevallier, Emilie Plantamura, Joël Doré, Anne Vekhoff, Simona Lapusan, Jerome Rey, Lila Gilis, Mohamad Mohty, Cyrielle Gasc, Françoise Isnard, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), MaaT Pharma [Lyon], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 788191,Homo.symbiosus, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Antibiotics, General Physics and Astronomy, Gut flora, Feces, 0302 clinical medicine, fluids and secretions, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, education.field_of_study, Multidisciplinary, biology, Myeloid leukemia, Fecal Microbiota Transplantation, Middle Aged, Anti-Bacterial Agents, 3. Good health, Leukemia, Treatment Outcome, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Acute Disease, Female, Adult, medicine.drug_class, Science, Population, Transplantation, Autologous, digestive system, Article, Phase II trials, Acute myeloid leukaemia, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, medicine, Humans, education, Aged, Bacteria, business.industry, Induction chemotherapy, General Chemistry, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, Transplantation, 030104 developmental biology, Immunology, Dysbiosis, business
Abstract: Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level., The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.
Published: 2021

6. High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice

Author: Magali Berland, Julie Cadiou, Florence Levenez, Nathalie Galleron, Benoît Quinquis, Florence Thirion, Franck Gauthier, Emmanuelle Le Chatelier, Florian Plaza Oñate, Carole Schwintner, Sylvie Rabot, Patricia Lepage, Dusko Ehrlich, Joël Doré, Catherine Juste, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and MaaT Pharma [Lyon]
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Science, Biology, Microbiology, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Animals, Germ-Free Life, Humans, Germ, Cryopreservation, Multidisciplinary, Fecal bacteriotherapy, Fecal Microbiota Transplantation, Fecal microbiota, Maltodextrin, Trehalose, Gastrointestinal Microbiome, Mice, Inbred C57BL, Family Lachnospiraceae, 030104 developmental biology, chemistry, Ready to use, Medicine, 030211 gastroenterology & hepatology, Metagenomics, Microbiome, Shotgun metagenomics
Abstract: The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.
Published: 2021

7. Adaptation of the gut pathobiont Enterococcus faecalis to deoxycholate and taurocholate bile acids

Author: Repoila, F., Le Bohec, F., Guérin, C., Lacoux, C., Tiwari, S., Jaiswal, A., Santana, M. Passos, Kennedy, Sean P., Quinquis, B., Rainteau, D., Juillard, V., Furlan, S., Bouloc, P., Nicolas, P., Miyoshi, A., Azevedo, V., Serror, P., MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis (MGP (US 1367)), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), INRAEUFMG'Science without borders' (CNPq), ANR-12-BSV6-0008,ReadRNA,Les transcriptomes bactériens primaires et maturés pour décrypter les réseaux de régulation(2012), Kennedy, Sean, and BLANC - Les transcriptomes bactériens primaires et maturés pour décrypter les réseaux de régulation - - ReadRNA2012 - ANR-12-BSV6-0008 - BLANC - VALID
Subjects: Taurocholic Acid, MESH: Enterococcus faecalis, MESH: Amino Acids, MESH: Humans, Multidisciplinary, MESH: Bile Acids and Salts, MESH: Deoxycholic Acid, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bile Acids and Salts, MESH: Dysbiosis, Enterococcus faecalis, Dysbiosis, Humans, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Amino Acids, MESH: Taurocholic Acid, Deoxycholic Acid
Abstract: Enterococcus faecalis is a natural inhabitant of the human gastrointestinal tract. This bacterial species is subdominant in a healthy physiological state of the gut microbiota (eubiosis) in adults, but can become dominant and cause infections when the intestinal homeostasis is disrupted (dysbiosis). The relatively high concentrations of bile acids deoxycholate (DCA) and taurocholate (TCA) hallmark eubiosis and dysbiosis, respectively. This study aimed to better understand how E. faecalis adapts to DCA and TCA. We showed that DCA impairs E. faecalis growth and possibly imposes a continuous adjustment in the expression of many essential genes, including a majority of ribosomal proteins. This may account for slow growth and low levels of E. faecalis in the gut. In contrast, TCA had no detectable growth effect. The evolving transcriptome upon TCA adaptation showed the early activation of an oligopeptide permease system (opp2) followed by the adjustment of amino acid and nucleotide metabolisms. We provide evidence that TCA favors the exploitation of oligopeptide resources to fuel amino acid needs in limiting oligopeptide conditions. Altogether, our data suggest that the combined effects of decreased DCA and increased TCA concentrations can contribute to the rise of E. faecalis population during dysbiosis.
Published: 2022

8. Both Disease Activity and HLA-B27 Status Are Associated With Gut Microbiome Dysbiosis in Spondyloarthritis Patients

Author: Magali Berland, Victoria Meslier, Samar Berreira Ibraim, Emmanuelle Le Chatelier, Nicolas Pons, Nicolas Maziers, Florence Thirion, Franck Gauthier, Florian Plaza Oñate, Jean‐Pierre Furet, Ariane Leboime, Roula Said‐Nahal, Florence Levenez, Nathalie Galleron, Benoît Quinquis, Philippe Langella, Stanislav Dusko Ehrlich, Maxime Breban, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AgroParisTech, Hôpital Ambroise Paré [AP-HP], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Assistance‐Hôpitaux de Paris (grant CRC‐2010), Fondation Arthritis Recherche & Développement, ANR-10-MIDI-0002,GEMISA,GEnétique, Microbiote, Inflammation, et Spondylarthrite Ankylosante(2010), and ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011)
Subjects: Rheumatology, [SDV]Life Sciences [q-bio], Immunology, Immunology and Allergy
Abstract: We gratefully acknowledge the kind contribution of Mrs. Nabila Yasmine Domingo-Saidji from the Clinical Research Unit of Paris Ile-de-France Ouest (URCPO), who supervised the administrative paperwork and helped us to manage ethical issues related to the study.; International audience; Objective: Gut microbiome dysbiosis has previously been reported in spondyloarthritis (SpA) patients and could be critically involved in the pathogenesis of this disorder. The objectives of this study were to further characterize the microbiota structure in SpA patients and to investigate the relationship between dysbiosis and disease activity in light of the putative influence of the genetic background. Methods: Shotgun sequencing was performed on fecal DNA isolated from stool samples from 2 groups of adult volunteers: SpA patients (n = 102) and healthy controls (n = 63). A subset of the healthy controls comprised the age-matched siblings of patients whose HLA–B27 status was known. Changes in gut microbiota composition were assessed based on species diversity, enterotypes, and taxonomic and functional differences. Results: Dysbiosis was confirmed in SpA patients as compared to healthy controls. The restriction of microbiota diversity was detected in patients with the most active disease, and the abundance of several bacterial species was correlated with Bath Ankylosing Spondylitis Disease Activity Index score. Among healthy controls, significant differences in microbiota composition were also detected between the HLA–B27–positive and the HLA–B27–negative siblings of SpA patients. We highlighted a decreased abundance of several species of bacteria in SpA patients, especially those bacteria belonging to the Clostridiales order. Among the few species of bacteria showing increased abundance, Ruminococcus gnavus was one of the top differentiating species. Conclusion: These findings reveal that genetic background and level of disease activity are likely to influence the composition of the gut microbiota of patients with SpA. It may be appropriate for further research on chronic arthritis to focus on these key parameters
Published: 2022

9. Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk

Author: Harimalala Ranaivo, Florence Thirion, Christel Béra-Maillet, Susie Guilly, Chantal Simon, Monique Sothier, Laurie Van Den Berghe, Nathalie Feugier-Favier, Stéphanie Lambert-Porcheron, Isabelle Dussous, Loïc Roger, Hugo Roume, Nathalie Galleron, Nicolas Pons, Emmanuelle Le Chatelier, Stanislav Dusko Ehrlich, Martine Laville, Joël Doré, Julie-Anne Nazare, CarMeN, laboratoire, Démonstrateurs - MetaGenoPolis - - MGP2011 - ANR-11-DPBS-0001 - DPBS - VALID, Intensity mapping of the atomic carbon CII line - CONCERTO - - Intensity mapping of the atomic carbon CII line: the promise of a new observational probe of dusty star-formation in post-reionization and reionization epoch2017-01-01 - 0000-00-00 - PE9, ERC-2017-ADG - VALID, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French-Clinical Research Infrastructure Network / F-CRIN [Lyon] (Cardiovascular & Renal Clinical Trialists - INI-CRCT ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bridor - Groupe LE DUFF [Rennes] (BGLD), This study was funded by Bridor and in part by Metagenopolis grant Agence Nationale de la Recherche ANR-11-DPBS-0001. JD acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement ERC-2017-AdG No. 788191 - Homo.symbiosus). We thank all the subjects who participated in this study. We thank Bernard Henrissat who annotated the IGC2 with CAZy., ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), European Project: PE9, ERC-2017-ADG, Intensity mapping of the atomic carbon CII line: the promise of a new observational probe of dusty star-formation in post-reionization and reionization epoch,Advanced Grant (AdG), PE9, ERC-2017-ADG,CONCERTO(2017), FCRIN/FORCE Network, Centre d'Edition Numérique Scientifique (CENS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)
Subjects: Microbiology (medical), Dietary Fiber, gut microbiota, [SDV]Life Sciences [q-bio], Gastroenterology, Dietary fiber diversity, Bread, Microbiology, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Infectious Diseases, Eisenbergiella sp, Cardiovascular Diseases, Parabacteroides distasonis, Metabolome, glycoside hydrolases, Humans, cardiometabolic profile
Abstract: International audience; Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q \textless 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (-0.42 mM; q \textless 0.01), LDL cholesterol (-0.36 mM; q \textless 0.01), insulin (-2.77 mIU/l; q \textless 0.05), and HOMA (-0.78; q \textless 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.
Published: 2022

10. Identification et quantification de souches microbiennes dans des échantillons métagénomiques par utilisation de graphes de variations

Author: da Silva, Kévin, Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes 1, Pierre Peterlongo, Nicolas Pons (co-encadrant), and Magali Berland (co-encadrante)
Subjects: Mapping, Read mapping, Metagenomics, Abondances au niveau souche, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Variation graphs, Graphes de variations, Strain-level abundances, Métagénomique
Abstract: Current studies are shifting from the use of single linear references to graph structures in order to represent multiple genomes. In parallel, resolving strain-level abundances within metagenomic samples is of growing interest for microbiome studies, as it would highlight new associations between strain variants and phenotypes that suggest major steps for diagnostic and therapeutic purposes. We developed StrainFLAIR that shows the use of variation graphs in this context by indexing highly similar genomic sequences as found with strains of a species, and we propose novel algorithmic solutions to identify and quantify strains in a set of sequenced genomes by querying this graph. We validated our approach first on simulated datasets which focused on a mixture of strains from a single species. The results show that StrainFLAIR was able to identify the present strains among the existing references, to detect new strains close to the existing references, and to estimate their relative abundances. We also validated StrainFLAIR on a mock composed of several species and strains. The results show again StrainFLAIR’s ability to profile correctly the sample even in this more complex configuration.; Les études actuelles se tournent vers l’utilisation de graphes au lieu de références linéaires afin de représenter plusieurs génomes. En parallèle, calculer les abondances des souches dans des échantillons métagénomiques suscite un intérêt croissant. Cela permettrait de mettre en évidence de nouvelles associations entre souches et phénotypes ouvrant des avancées pour le diagnostique et thérapeutiques. Nous avons développé StrainFLAIR, démontrant l’utilisation de graphes de variations dans ce contexte en indexant des séquences génomiques similaires telles que retrouvées entre souches d’une même espèce, et nous proposons de nouvelles solutions algorithmiques afin d’identifier et quantifier les souches à partir d’un ensemble de génomes séquencés en requêtant le graphe. Nous avons validé notre approche sur des données simulées constituées d’un mélange de souches d’une seule espèce. Les résultats montrent que StrainFLAIR a pu identifier les souches présentes dans l’échantillon parmi les références utilisées, détecter la présence de nouvelles souches proches de ces références, et estimer les abondances de ces souches. Nous avons également validé notre approche sur un mock composé de plusieurs espèces et souches. Les résultats montrent à nouveau que StrainFLAIR a pu profiler correctement l’échantillon même dans une configuration plus complexe.
Published: 2022

11. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author: Sebastien Fromentin, Sofia K. Forslund, Kanta Chechi, Judith Aron-Wisnewsky, Rima Chakaroun, Trine Nielsen, Valentina Tremaroli, Boyang Ji, Edi Prifti, Antonis Myridakis, Julien Chilloux, Petros Andrikopoulos, Yong Fan, Michael T. Olanipekun, Renato Alves, Solia Adiouch, Noam Bar, Yeela Talmor-Barkan, Eugeni Belda, Robert Caesar, Luis Pedro Coelho, Gwen Falony, Soraya Fellahi, Pilar Galan, Nathalie Galleron, Gerard Helft, Lesley Hoyles, Richard Isnard, Emmanuelle Le Chatelier, Hanna Julienne, Lisa Olsson, Helle Krogh Pedersen, Nicolas Pons, Benoit Quinquis, Christine Rouault, Hugo Roume, Joe-Elie Salem, Thomas S. B. Schmidt, Sara Vieira-Silva, Peishun Li, Maria Zimmermann-Kogadeeva, Christian Lewinter, Nadja B. Søndertoft, Tue H. Hansen, Dominique Gauguier, Jens Peter Gøtze, Lars Køber, Ran Kornowski, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Serge Hercberg, Ivica Letunic, Fredrik Bäckhed, Jean-Michel Oppert, Jens Nielsen, Jeroen Raes, Peer Bork, Michael Stumvoll, Eran Segal, Karine Clément, Marc-Emmanuel Dumas, S. Dusko Ehrlich, Oluf Pedersen, Commission of the European Communities, Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Molecular Biology Laboratory [Heidelberg] (EMBL), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitätsklinikum Leipzig, IT University of Copenhagen (ITU), University of Gothenburg (GU), Chalmers University of Technology [Göteborg], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Imperial College London, Guangzhou Medical University, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Our study, Metagenomics in Cardiometabolic Diseases, with the acronym METACARDIS, was sponsored by the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312. Assistance Publique-Hôpitaux de Paris is the promoter of the clinical investigation. Parts of the studies were also supported by Metagenopolis grant ANR-11-DPBS-0001, the Leducq Foundation, the Novo Nordisk Foundation and the NIHR Imperial Biomedical Research Centre and by grants from the French National Research Agency (ANR-10-LABX-46 (European Genomics Institute for Diabetes)), the National Center for Precision Diabetic Medicine, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001), the European Union (FEDER), the Hauts-de-France Regional Council (Agreement 20001891/NP0025517), the European Metropolis of Lille (agreement 2019_ESR_11) and site ULNE (R-002-20-TALENT-DUMAS), which is also jointly funded by ANR (ANR-16-IDEX-0004-ULNE), the Hauts-de-France Regional Council (20002845) and the European Metropolis of Lille. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research institution at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation. K. Chechi is supported by the Medical Research Council Skills Development Fellowship (grant no. MR/S020039/1) and the Wellcome Trust-funded Institutional Strategic Support Fellowship (grant no. 204834/Z/16/Z). L.H. was in receipt of a Medical Research Council Intermediate Research Fellowship in Data Science (grant no. MR/L01632X/1, UK Med-Bio). S.K.F. was supported by the German Centre for Cardiovascular Research, the German Research Council (projects SFB1365, SFB1470 and KFO339) and the German Ministry of Education and Research., We are indebted to the MetaCardis study participants and patient associations (Alliance du Coeur and CNAO) for their input and interface. Similarly, we are indebted to the MetaCardis consortium (http://www.metacardis.net/) collaborators for contributions at multiple levels since the consortium start in 2012. A full list of collaborators is given in the Supplementary Information. We further thank D. Bonnefont-Rousselot (Department of Metabolic Biochemistry, Pitié-Salpêtrière Hospital) for the analysis of plasma lipid profiles. We greatly appreciate the assistance of nurses, dietitians, laboratory technicians, clinical research assistants and data managers at the Novo Nordisk Foundation Center for Basic Metabolic Research, the Clinical Research Unit at Fredriksberg and Bispebjerg Hospitals, Copenhagen, the Clinical Investigation Platform at the Institute of Cardiometabolism and Nutrition for Patient Investigations and the Clinical Investigation Center from Pitié-Salpêtrière Hospital, Paris, and the University of Leipzig Medical Center, Leipzig. Quanta Medical provided regulatory oversight of the clinical study and contributed to the processing and management of electronic data, ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), ANR-16-IDEX-0004,ULNE,ULNE(2016), European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Biochemistry & Molecular Biology, IMPACT, [SDV]Life Sciences [q-bio], Immunology, Research & Experimental Medicine, General Biochemistry, Genetics and Molecular Biology, SERUM, Humans, Longitudinal Studies, cardiovascular diseases, SIGNATURES, 11 Medical and Health Sciences, P-CRESOL, RISK, Science & Technology, PLASMA, Microbiota, GUT MICROBIOTA, General Medicine, Cell Biology, Middle Aged, Medicine, Research & Experimental, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, Cardiovascular Diseases, Metabolome, CORONARY-ARTERY-DISEASE, HEART, HEALTH, Life Sciences & Biomedicine
Abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features. ispartof: NATURE MEDICINE vol:28 issue:2 pages:303-+ ispartof: location:United States status: published
Published: 2022

12. Long-term diosmectite use does not alter the gut microbiota in adults with chronic diarrhea

Author: Kévin Da Silva, Susie Guilly, Florence Thirion, Emmanuelle Le Chatelier, Nicolas Pons, Hugo Roume, Benoît Quinquis, Stanislav D. Ehrlich, Nassima Bekkat, Hélène Mathiex-Fortunet, Harry Sokol, Joël Doré, Université Paris-Saclay, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ipsen [Boulogne Billancourt] (Ipsen), IPSEN, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Malbec, Odile
Subjects: Adult, Diarrhea, Male, Microbiology (medical), Shotgun metagenomics, Adolescent, [SDV]Life Sciences [q-bio], Gut microbiota, Microbiology, Trial registration: Clinicaltrials.gov NCT03 045926 Smecta ®, Feces, Young Adult, Smecta®, Humans, Chronic diarrhea, Bacteria, Silicates, Middle Aged, Diosmectite, QR1-502, Watery stools, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Loose stools, Chronic Disease, Metagenome, Female, Microbiota composition, Long-term diosmectite use
Abstract: Background Diosmectite, a natural colloidal clay, has been used worldwide for a number of approved indications, including the treatment of chronic functional diarrhea. Here, we used high-resolution whole metagenome shotgun sequencing to assess the impact of a 5 weeks administration of diosmectite (3 g/sachet, 3 sachets/day) on the fecal microbiota of 35 adults with functional chronic diarrhea. Results Gut microbiota was not impacted by diosmectite administration. In particular, richness remained stable and no microbial species displayed a significant evolution. Segregating patients either by diosmectite response (non responder, early responder, late responder) or by nationality (Great-Britain or Netherlands) yielded the same results. Conclusion We concluded that no microbiota-related physiological alterations are expected upon long-term treatment with diosmectite. Trial registration Clinicaltrials.gov NCT03045926
Published: 2022

13. Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease

Author: Yeela Talmor-Barkan, Noam Bar, Aviv A. Shaul, Nir Shahaf, Anastasia Godneva, Yuval Bussi, Maya Lotan-Pompan, Adina Weinberger, Alon Shechter, Chava Chezar-Azerrad, Ziad Arow, Yoav Hammer, Kanta Chechi, Sofia K. Forslund, Sebastien Fromentin, Marc-Emmanuel Dumas, S. Dusko Ehrlich, Oluf Pedersen, Ran Kornowski, Eran Segal, European Molecular Biology Laboratory [Heidelberg] (EMBL), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Department of Computer Science and Applied Mathematics, Weizman Institute of Science Rehovot, ANR-16-IDEX-0004,ULNE,ULNE(2016), and ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018)
Subjects: Bacteria, Risk Factors, Microbiota, [SDV]Life Sciences [q-bio], Metabolome, Humans, Metabolomics, Coronary Artery Disease, General Medicine, Acute Coronary Syndrome, General Biochemistry, Genetics and Molecular Biology
Abstract: Complex diseases, such as coronary artery disease (CAD), are often multifactorial, caused by multiple underlying pathological mechanisms. Here, to study the multifactorial nature of CAD, we performed comprehensive clinical and multi-omic profiling, including serum metabolomics and gut microbiome data, for 199 patients with acute coronary syndrome (ACS) recruited from two major Israeli hospitals, and validated these results in a geographically distinct cohort. ACS patients had distinct serum metabolome and gut microbial signatures as compared with control individuals, and were depleted in a previously unknown bacterial species of the Clostridiaceae family. This bacterial species was associated with levels of multiple circulating metabolites in control individuals, several of which have previously been linked to an increased risk of CAD. Metabolic deviations in ACS patients were found to be person specific with respect to their potential genetic or environmental origin, and to correlate with clinical parameters and cardiovascular outcomes. Moreover, metabolic aberrations in ACS patients linked to microbiome and diet were also observed to a lesser extent in control individuals with metabolic impairment, suggesting the involvement of these aberrations in earlier dysmetabolic phases preceding clinically overt CAD. Finally, a metabolomics-based model of body mass index (BMI) trained on the non-ACS cohort predicted higher-than-actual BMI when applied to ACS patients, and the excess BMI predictions independently correlated with both diabetes mellitus (DM) and CAD severity, as defined by the number of vessels involved. These results highlight the utility of the serum metabolome in understanding the basis of risk-factor heterogeneity in CAD.
Published: 2022

14. Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Author: Zhiqiang Sha, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Boris Bernhardt, Sven Bolte, Geraldo F. Busatto, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Meiyu Duan, Fabio Luis Souza Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Jacqueline Fitzgerald, Dorothea L. Floris, Barbara Franke, Christine M. Freitag, Louise Gallagher, David C. Glahn, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Luisa Lazaro, Beatriz Luna, Jane McGrath, Sarah E. Medland, Filippo Muratori, Declan G. M. Murphy, Janina Neufeld, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Jose C. Pariente, Merel C. Postema, Karl Lundin Remnelius, Alessandra Retico, Pedro Gomes Penteado Rosa, Katya Rubia, Devon Shook, Kristiina Tammimies, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of Toronto, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Stockholm Health Care Services (SLSO), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Universidade de São Paulo = University of São Paulo (USP), University of Pisa - Università di Pisa, Department of Child and Adolescent Psychiatry and Psychology, Centro de Investigación Biomédica en Red de Salut Mental (CIBER-SAM Network), Hospital Clinic Barcelona, King‘s College London, University Medical Center [Utrecht], Goethe-Universität Frankfurt am Main, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oregon Health and Science University [Portland] (OHSU), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, and McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada]
Subjects: Neuroinformatics, Biochemistry & Molecular Biology, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], CHILDREN, ORGANIZATION, ACTIVATION, Cellular and Molecular Neuroscience, CONNECTIVITY, 130 000 Cognitive Neurology & Memory, CEREBRAL-CORTEX, Neural Pathways, Humans, HETEROGENEITY, Molecular Biology, 11 Medical and Health Sciences, Psychiatry, Cerebral Cortex, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, LANGUAGE LATERALIZATION, Neurosciences, Brain, 06 Biological Sciences, Magnetic Resonance Imaging, 17 Psychology and Cognitive Sciences, Psychiatry and Mental health, INDIVIDUALS, MORPHOMETRY, Neurosciences & Neurology, Life Sciences & Biomedicine, CORTICAL THICKNESS
Abstract: Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.
Published: 2022

15. A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti–PD-1 Resistance through Effects on the Gut Microbiota

Author: Meriem Messaoudene, Reilly Pidgeon, Corentin Richard, Mayra Ponce, Khoudia Diop, Myriam Benlaifaoui, Alexis Nolin-Lapalme, Florent Cauchois, Julie Malo, Wiam Belkaid, Stephane Isnard, Yves Fradet, Lharbi Dridi, Dominique Velin, Paul Oster, Didier Raoult, François Ghiringhelli, Romain Boidot, Sandy Chevrier, David T. Kysela, Yves V. Brun, Emilia Liana Falcone, Geneviève Pilon, Florian Plaza Oñate, Oscar Gitton-Quent, Emmanuelle Le Chatelier, Sylvere Durand, Guido Kroemer, Arielle Elkrief, André Marette, Bastien Castagner, Bertrand Routy, COMBE, Isabelle, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), McGill University = Université McGill [Montréal, Canada], McGill University Health Center [Montreal] (MUHC), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Université Laval [Québec] (ULaval), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Gustave Roussy (IGR), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and École Pratique des Hautes Études (EPHE)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Bacteria, Polyphenols, Fecal Microbiota Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mice, Oncology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti–PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti–PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti–PD-1 resistance. Significance: The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti–PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873
Published: 2022

16. Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis

Author: Levast, Benoît, Fontaine, Mathieu, Nancey, Stéphane, Dechelotte, Pierre, Doré, Joël, Lehert, Philippe, MaaT Pharma [Lyon], Questel Consulting, Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Melbourne, and Université Catholique de Louvain = Catholic University of Louvain (UCL)
Subjects: Fecal Microbiota, [SDV]Life Sciences [q-bio], Gastroenterology, Ulcerative Colitis, Single-Donor
Abstract: International audience; Introduction: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation.Methods: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach.Results: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models.Discussion: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.
Published: 2023

17. Combinatorial, additive and dose-dependent drug-microbiome associations

Author: Forslund, SK, Chakaroun, R, Zimmermann-Kogadeeva, M, Markó, L, Aron-Wisnewsky, J, Nielsen, T, Moitinho-Silva, L, Schmidt, TSB, Falony, G, Vieira-Silva, S, Adriouch, S, Alves, RJ, Assmann, K, Bastard, J-P, Birkner, T, Caesar, R, Chilloux, J, Coelho, LP, Fezeu, L, Galleron, N, Helft, G, Isnard, R, Ji, B, Kuhn, M, Le Chatelier, E, Myridakis, A, Olsson, L, Pons, N, Prifti, E, Quinquis, B, Roume, H, Salem, J-E, Sokolovska, N, Tremaroli, V, Valles-Colomer, M, Lewinter, C, Søndertoft, NB, Pedersen, HK, Hansen, TH, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Batisse, J-P, Belda, E, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Collet, J-P, Dao, M-C, Djebbar, M, Doré, A, Engelbrechtsen, L, Fellahi, S, Fromentin, S, Galan, P, Gauguier, D, Giral, P, Hartemann, A, Hartmann, B, Holst, JJ, Hornbak, M, Hoyles, L, Hulot, J-S, Jaqueminet, S, Jørgensen, NR, Julienne, H, Justesen, J, Kammer, J, Krarup, N, Kerneis, M, Khemis, J, Kozlowski, R, Lejard, V, Levenez, F, Lucas-Martini, L, Massey, R, Martinez-Gili, L, Maziers, N, Medina-Stamminger, J, Montalescot, G, Moute, S, Neves, AL, Olanipekun, M, Le Pavin, LP, Poitou, C, Pousset, F, Pouzoulet, L, Rodriguez-Martinez, A, Rouault, C, Silvain, J, Svendstrup, M, Swartz, T, Vanduyvenboden, T, Vatier, C, Walther, S, Gøtze, JP, Køber, L, Vestergaard, H, Hansen, T, Zucker, J-D, Hercberg, S, Oppert, J-M, Letunic, I, Nielsen, J, Bäckhed, F, Ehrlich, SD, Dumas, M-E, Raes, J, Pedersen, O, Clément, K, Stumvoll, M, Bork, P, The MetaCardis Consortium (Hoyles, L.), European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (UCPH), University of New South Wales [Sydney] (UNSW), Paul Scherrer Institute (PSI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Heidelberg University, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Gothenburg (GU), Imperial College London, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chalmers University of Technology [Gothenburg, Sweden], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Biobyte Solutions [Heidelberg, Germany] (BS), IT University of Copenhagen (ITU), Sahlgrenska University Hospital [Gothenburg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, McGill University and Genome Quebec Innovation Centre, Helmholtz Institute Ulm (HIU), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Würzburg = Universität Würzburg, Yonsei University, MetaCardis Consortium*: Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin, Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann, Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles, Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura Martinez-Gili, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault, Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Dumas, Marc-Emmanuel, Universität Leipzig [Leipzig], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Henri Mondor, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-1901(ex CIC-1421)), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK
Subjects: Clostridiales, Science & Technology, Multidisciplinary, ANTIBIOTIC USE, IMPACT, Microbiota, [SDV]Life Sciences [q-bio], HUMAN GUT MICROBIOME, Atherosclerosis, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, PROTON PUMP INHIBITORS, Cardiovascular and Metabolic Diseases, GUIDELINE, Metabolome, MANAGEMENT, Humans, Science & Technology - Other Topics, ALTERS
Abstract: During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. ispartof: NATURE vol:600 issue:7889 pages:500-+ ispartof: location:England status: published
Published: 2021

18. Author Correction: Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Author: Merel C. Postema, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Geraldo Busatto Filho, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Adriana Di Martino, Ilan Dinstein, Fabio Luis S. Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Xin Feng, Jackie Fitzgerald, Dorothea L. Floris, Christine M. Freitag, Louise Gallagher, David C. Glahn, Ilaria Gori, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Xiang Zhen Kong, Luisa Lazaro, Jason P. Lerch, Beatriz Luna, Mauricio M. Martinho, Jane McGrath, Sarah E. Medland, Filippo Muratori, Clodagh M. Murphy, Declan G. M. Murphy, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Olga Puig, Alessandra Retico, Pedro Rosa, Katya Rubia, Devon Shook, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of Toronto, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Pisa - Università di Pisa, Department of Child and Adolescent Psychiatry and Psychology, Centro de Investigación Biomédica en Red de Salut Mental (CIBER-SAM Network), Hospital Clinic Barcelona, King‘s College London, NYU Langone Medical Center, Utrecht University [Utrecht], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oregon Health and Science University [Portland] (OHSU), School of Management, Fujian Agriculture and Forestry University (FAFU), and Goethe-University Frankfurt am Main
Subjects: Adult, Male, Adolescent, Autism Spectrum Disorder, Science, [SDV]Life Sciences [q-bio], Prefrontal Cortex, General Physics and Astronomy, Gyrus Cinguli, General Biochemistry, Genetics and Molecular Biology, Young Adult, Humans, Author Correction, Child, Cerebral Cortex, Multidisciplinary, Brain, Organ Size, General Chemistry, Autism spectrum disorders, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Case-Control Studies, Female, Neuroscience
Abstract: Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.
Published: 2021

19. l1-spectral clustering algorithm: a spectral clustering method using l1-regularization

Author: Champion, Camille, Champion, Magali, Blazère, Mélanie, Burcelin, Rémy, Loubes, Jean-Michel, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Champion, Camille, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: ComputingMethodologies_PATTERNRECOGNITION, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Biological networks, Spectral clustering, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], Unsupervised learning, l1-penalty
Abstract: Detecting cluster structure is a fundamental task to understand and visualize functional characteristics of a graph. Among the different clustering methods available, spectral clustering is one of the most widely used due to its speed and simplicity, while still being sensitive to perturbations imposed on the graph. In this paper, we present a variant of the spectral clustering algorithm, called l1-spectral clustering, based on Lasso regularization and adapted to perturbed graph models. Contrary to the spectral clustering, this procedure does not require the use of the k-means: it detects the hidden natural cluster structure of the graph by promoting sparse eigenbases solutions of specific l1-minimization problems. The effectiveness and robustness to noise perturbations of the l1-spectral clustering algorithm is confirmed through a collection of simulated and real biological data.
Published: 2021

20. Human and preclinical studies of the host–gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health

Author: Petros Andrikopoulos, Fatima Djouadi, Lesley Hoyles, Trine Nielsen, Matej Orešič, Karine Clément, Nicolas Pons, Andrea Rodriguez-Martinez, Sofia K. Forslund, Gwen Falony, Francois Brial, Stanislav Dusko Ehrlich, Tuulia Hyötyläinen, Dominique Gauguier, Peer Bork, Marc-Emmanuel Dumas, Michael Olanipekun, Ana Luisa Neves, Jeroen Raes, Julien Chilloux, Jeremy K. Nicholson, Sara Vieira-Silva, Torben Hansen, Emmanuelle Le-chatelier, Aurélie Le Lay, Oluf Pedersen, Ghiwa Ishac Mouawad, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Imperial College London, University of Copenhagen = Københavns Universitet (UCPH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Nottingham Trent University, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Delbrück Centrum für Molekulare Medizin (MDC), Örebro University, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), European Molecular Biology Laboratory [Heidelberg] (EMBL), King‘s College London, Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), McGill University = Université McGill [Montréal, Canada], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (KU), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Max-Delbrück-Centrum für Molekulare Medizin [Berlin, Germany] (MDC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Dumas, Marc-Emmanuel, Medical Research Council (MRC), and Commission of the European Communities
Subjects: Male, 0301 basic medicine, obesity, Magnetic Resonance Spectroscopy, IMPACT, Denmark, Metabolite, Saturated fat, [SDV]Life Sciences [q-bio], DIVERSITY, intestinal microbiology, Urine, PHENOTYPE, SERUM, Mice, chemistry.chemical_compound, 0302 clinical medicine, RICHNESS, Prevotella, Gut Microbiota, colonic microflora, 2. Zero hunger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology, Hippurates, Gastroenterology, Biodiversity, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, CATALOG, Phenotype, 030220 oncology & carcinogenesis, Metabolome, Female, Enterotype, Life Sciences & Biomedicine, medicine.medical_specialty, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, GENES, glucose metabolism, Context (language use), Carbohydrate metabolism, DIET, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, REVEALS, medicine, Animals, Humans, Science & Technology, Gastroenterology & Hepatology, 1103 Clinical Sciences, biology.organism_classification, Gastrointestinal Microbiome, 030104 developmental biology, Endocrinology, chemistry, Cardiovascular and Metabolic Diseases, 1114 Paediatrics and Reproductive Medicine, RAT, Metagenomics, Bacteroides, Biomarkers
Abstract: ObjectiveGut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health.DesignIn 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes.ResultsIn the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion.ConclusionOur human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
Published: 2021

21. Protein Intake, Metabolic Status and the Gut Microbiota in Different Ethnicities: Results from Two Independent Cohorts

Author: Pierre Bel Lassen, Ilias Attaye, Solia Adriouch, Mary Nicolaou, Judith Aron-Wisnewsky, Trine Nielsen, Rima Chakaroun, Emmanuelle Le Chatelier, Sofia Forslund, Eugeni Belda, Peer Bork, Fredrik Bäckhed, Michael Stumvoll, Oluf Pedersen, Hilde Herrema, Albert K. Groen, Sara-Joan Pinto-Sietsma, Aeilko H. Zwinderman, Max Nieuwdorp, Karine Clement, on behalf of Metacardis Consortium, Internal medicine, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Universitätsklinikum Leipzig, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Integrative Phenomics [Paris], European Molecular Biology Laboratory [Heidelberg] (EMBL), Gestionnaire, Hal Sorbonne Université, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), and University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)
Subjects: Adult, DNA, Bacterial, Male, HELIUS study, Gut microbiota, digestive system, Article, Feces, protein diet, Ethnicity, Humans, TX341-641, Aged, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, gut microbiota, diabetes, Nutrition. Foods and food supply, Diabetes, Racial Groups, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Protein diet, Diet, Gastrointestinal Microbiome, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular and Metabolic Diseases, ethnicity, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Dietary Proteins, Energy Metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, human activities
Abstract: Background: Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethnicity. However, to date most studies have predominantly focused on carbohydrate and fiber intake with regards to metabolic status and gut microbiota composition. Objectives: To determine the associations between dietary protein intake, gut microbiota composition, and metabolic status in different ethnicities. Methods: Separate cross-sectional analysis of two European cohorts (MetaCardis, n = 1759, HELIUS, n = 1528) including controls, patients with pre-T2D, and patients with T2D of Caucasian/non-Caucasian origin with nutritional data obtained from Food Frequency Questionnaires and gut microbiota composition. Results: In both cohorts, animal (but not plant) protein intake was associated with pre-T2D status and T2D status after adjustment for confounders. There was no significant association between protein intake (total, animal, or plant) with either gut microbiota alpha diversity or beta diversity, regardless of ethnicity. At the species level, we identified taxonomical signatures associated with animal protein intake that overlapped in both cohorts with different abundances according to metabolic status and ethnicity. Conclusions: Animal protein intake is associated with pre-T2D and T2D status but not with gut microbiota beta or alpha diversity, regardless of ethnicity. Gut microbial taxonomical signatures were identified, which could function as potential modulators in the association between dietary protein intake and metabolic status.
Published: 2021
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22. Bacterial Consumption of T4 Phages

Author: Godon, Jean-Jacques, Bize, Ariane, Ngo, Hoang, Cauquil, Laurent, Almeida, Mathieu, Petit, Marie-Agnès, Zemb, Olivier, Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Procédés biotechnologiques au service de l'environnement (UR PROSE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: bacteriophage, QH301-705.5, [SDE.IE]Environmental Sciences/Environmental Engineering, viruses, food and beverages, Aeromonas, Biology (General), stable isotope probing, Article
Abstract: The bacterial consumption of viruses not been reported on as of yet even though bacteria feed on almost anything. Viruses are widely distributed but have no acknowledged active biocontrol. Viral biomass undoubtedly reintegrates trophic cycles, however, the mechanisms of this phase still remain unknown. 13C-labelled T4 phages monitor the increase of the density of the bacterial DNA concomitant with the decrease of plaque forming units. We used 12C T4 phages as a control. T4 phage disappearance in wastewater sludge was found to occur mainly through predation by Aeromonadacea. Phage consumption also favours significant in situ bacterial growth. Furthermore, an isolated strain of Aeromonas was observed to grow on T4 phages as sole the source of carbon, nitrogen, and phosphorus. Bacterial species are capable of consuming bacteriophages in situ, which is likely a widespread and underestimated type of biocontrol. This assay is anticipated as a starting point for harnessing the bacterial potential in limiting the diffusion of harmful viruses within environments such as in the gut or in water.
Published: 2021

23. A combined test for feature selection on sparse metaproteomics data - alternative to missing value imputation

Author: Sandra Plancade, Ariane Bassignani, Blein Nicolas M, Catherine Juste, Olivier Langella, Berland M, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), and AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0303 health sciences, Computer science, General Neuroscience, Univariate, Experimental data, Context (language use), Feature selection, General Medicine, Missing data, computer.software_genre, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, [STAT]Statistics [stat], 010104 statistics & probability, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Metaproteomics, Combined test, Statistics::Methodology, Imputation (statistics), Data mining, 0101 mathematics, General Agricultural and Biological Sciences, computer, 030304 developmental biology
Abstract: One of the difficulties encountered in the statistical analysis of metaproteomics data is the high proportion of missing values, which are usually treated by imputation. Nevertheless, imputation methods are based on restrictive assumptions regarding missingness mechanisms, namely “at random” or “not at random”. To circumvent these limitations in the context of feature selection in a multi-class comparison, we propose a univariate selection method that combines a test of association between missingness and classes, and a test for difference of observed intensities between classes. This approach implicitly handles both missingness mechanisms. We performed a quantitative and qualitative comparison of our procedure with imputation-based feature selection methods on two experimental data sets, as well as simulated data with various scenarios regarding the missingness mechanisms and the nature of the difference of expression (differential intensity or differential missingness). Whereas we observed similar performances in terms of prediction on the experimental data set, the feature ranking and selection from various imputation-based methods were strongly divergent. We showed that the combined test reaches a compromise by correlating reasonably with other methods, and remains efficient in all simulated scenarios unlike imputation-based feature selection methods.
Published: 2021

24. Multifaceted modes of action of the anticancer probiotic Enterococcus hirae

Author: Marion Leduc, Didier Raoult, Laura Mondragón, Kristina Iribarren, Anne-Gaëlle Goubet, Diane Derrien, Satoru Yonekura, Noélie Bossut, Valerio Iebba, Nicola Segata, Guo Chen, Ivo G. Boneca, Lisa Derosa, Adrien Joseph, Fabrice Andre, Sylvère Durand, Aurélie Fluckiger, Maryam Tidjani Alou, Fanny Aprahamian, Richard J. Wheeler, Maryse Moya-Nilges, Eugenie Pizzato, Bo Qu, Guido Kroemer, Oliver Kepp, Nicolas Pons, Romain Daillère, Fabien Lemaitre, Laurence Zitvogel, Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Shanghai Jiao Tong University [Shanghai], Institut Gustave Roussy (IGR), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, UMR 1015 Immunologie des tumeurs et immunothérapie contre le cancer (ITIC), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Trento [Trento], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska University Hospital [Stockholm], Fondation pour la Recherche Médicale, Ligue contre le Cancer (équipes labellisées), Leducq Foundation, Seerave Foundation, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC Cancer Research and Personalized Medicine (CARPEM), Fondation ARC pour la Recherche sur le Cancer, Région Ile-de-France, Chancellerie des universités de Paris (Legs Poix), FRM, European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR), Gustave Roussy Odyssea, Fondation Carrefour, High-end Foreign Expert Program in China: GDW20171100085 and GDW20181100051, Institut National du Cancer (INCA) France, Inserm (HTE), Institut Universitaire de France, ANR-10-COHO-0004,CANTO,Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cancer(2010), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 680969,H2020,H2020-HCO-2015,ERA-CVD(2015), European Project: 825410, H2020-EU.3.1., H2020-EU.3.1.2.,ONCOBIOME (2019), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Ligue Nationale Contre le Cancer (LNCC), Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Goubet, A. -G., Wheeler, R., Fluckiger, A., Qu, B., Lemaitre, F., Iribarren, K., Mondragon, L., Tidjani Alou, M., Pizzato, E., Durand, S., Derosa, L., Aprahamian, F., Bossut, N., Moya-Nilges, M., Derrien, D., Chen, G., Leduc, M., Joseph, A., Pons, N., Le Chatelier, E., Segata, N., Yonekura, S., Iebba, V., Kepp, O., Raoult, D., Andre, F., Kroemer, G., Boneca, I. G., Zitvogel, L., Daillere, R., Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité (UPC), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and European Project: 825410,ONCOBIOME
Subjects: 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], microbiome, law.invention, Probiotic, Mice, 0302 clinical medicine, Cancer immunotherapy, Enterococcus hirae, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neoplasms, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, CD137, 3. Good health, Bifidobacterium animalis, Anti-Bacterial Agents, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, immunotherapy, Immunotherapy, microbiota, cancer, tumor, probiotic, intratumoral IFNγ, Biology, Article, Microbiology, 03 medical and health sciences, Memory T Cells, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Microbiome, Molecular Biology, Probiotics, Autophagy, Cell Biology, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, Mice, Inbred C57BL, 030104 developmental biology, Dysbiosis
Abstract: International audience; A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFN gamma-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.
Published: 2021

25. Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection

Author: Benoît Levast, Nicolas Benech, Cyrielle Gasc, Cécile Batailler, Eric Senneville, Sébastien Lustig, Cécile Pouderoux, David Boutoille, Lilia Boucinha, Frederic-Antoine Dauchy, Valérie Zeller, Marianne Maynard, Charles Cazanave, Thanh-Thuy Le Thi, Jérôme Josse, Joël Doré, Frederic Laurent, Tristan Ferry, MaaT Pharma [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Université de Lille, Service Régional Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, Université de Nantes (UN), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), USC EA 3671, infections humaines à mycoplasmes et chlamydiae, Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This study was funded by MaaT Pharma (http://www.maatpharma.com) as part of the Concours Mondial de l'Innovation funded by Banque Publique d'Investissement-France., Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_specialty, Bone and joint infection, medicine.drug_class, 030106 microbiology, Antibiotics, Gut microbiota, Gut flora, Gastroenterology, Antimicrobial therapy, 03 medical and health sciences, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Microbiome, Prospective cohort study, Feces, Original Research, lcsh:R5-920, biology, business.industry, Neopterin, General Medicine, biology.organism_classification, Antimicrobial, medicine.disease, 3. Good health, 030104 developmental biology, chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Medicine, Dysbiosis, business, lcsh:Medicine (General)
Abstract: There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray–Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray–Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r2 = 0.17; p < 0.0001). The PCoA analysis of the Bray–Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.
Published: 2021

26. StrainFLAIR: strain-level profiling of metagenomic samples using variation graphs

Author: Da Silva, Kévin, Pons, Nicolas, Berland, Magali, Plaza Oñate, Florian, Almeida, Mathieu, Peterlongo, Pierre, Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Région Bretagne, France., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: strain-level, Bioinformatics, Medicine, identification, Read mapping, Genomics, Metagenomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Variation graphs, Microbiology, Strain-level abundances
Abstract: International audience; Current studies are shifting from the use of single linear references to representation of multiple genomes organised in pangenome graphs or variation graphs. Meanwhile, in metagenomic samples, resolving strain-level abundances is a major step in microbiome studies, as associations between strain variants and phenotype are of great interest for diagnostic and therapeutic purposes. We developed StrainFLAIR with the aim of showing the feasibility of using variation graphs for indexing highly similar genomic sequences up to the strain level, and for characterizing a set of unknown sequenced genomes by querying this graph. On simulated data composed of mixtures of strains from the same bacterial species Escherichia coli, results show that StrainFLAIR was able to distinguish and estimate the abundances of close strains, as well as to highlight the presence of a new strain close to a referenced one and to estimate its abundance. On a real dataset composed of a mix of several bacterial species and several strains for the same species, results show that in a more complex configuration StrainFLAIR correctly estimates the abundance of each strain. Hence, results demonstrated how graph representation of multiple close genomes can be used as a reference to characterize a sample at the strain level.
Published: 2021

27. The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome

Author: Tal Korem, B. Brett Finlay, Philippe Gros, Naama Geva-Zatorsky, Maria Gloria Dominguez-Bello, Martin J. Blaser, Frédéric Keck, Meghan B. Azad, Karen Guillemin, Eran Elinav, Katherine R. Amato, Hiutung Chu, Stanislav Dusko Ehrlich, Liping Zhao, Tamara Giles-Vernick, Mark Nichter, Tobias Rees, Hendrik N. Poinar, Melissa K. Melby, Sven Pettersson, Thomas C. G. Bosch, Margaret J. McFall-Ngai, Carolina Tropini, University of British Columbia (UBC), Canadian Institute for Advanced Research (CIFAR), Northwestern University [Evanston], Children's Hospital Research Institute of Manitoba [Winnipeg, Canada], University of Manitoba [Winnipeg], Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), Kiel University, University of California [San Diego] (UC San Diego), University of California, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Weizmann Institute of Science [Rehovot, Israël], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Technion - Israel Institute of Technology [Haifa], McGill University = Université McGill [Montréal, Canada], University of Oregon [Eugene], Laboratoire d'anthropologie sociale (LAS), École des hautes études en sciences sociales (EHESS)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], University of Hawai'i [Honolulu] (UH), University of Delaware [Newark], University of Arizona, Nanyang Technological University [Singapour], McMaster University [Hamilton, Ontario], Berggruen Institute [Los Angeles, California], Anthropologie et écologie de l’émergence des maladies - Anthropology and Ecology of Disease Emergence, Institut Pasteur [Paris], University of California (UC), and Institut Pasteur [Paris] (IP)
Subjects: Male, media_common.quotation_subject, Physical Distancing, MESH: Anti-Infective Agents, microbiome, Disease, Biology, Affect (psychology), MESH: Eating, hygiene hypothesis, [SHS]Humanities and Social Sciences, Eating, 03 medical and health sciences, MESH: Infection Control, 0302 clinical medicine, MESH: Pregnancy, Anti-Infective Agents, Hygiene hypothesis, Pregnancy, Hygiene, Environmental health, Pandemic, Humans, MESH: COVID-19, MESH: Microbiota, 030212 general & internal medicine, Microbiome, Aged, 030304 developmental biology, media_common, MESH: Aged, Infection Control, 0303 health sciences, MESH: Humans, Multidisciplinary, MESH: Physical Distancing, Microbiota, Human microbiome, Infant, COVID-19, MESH: Infant, Biosocial theory, MESH: Male, 3. Good health, MESH: Hygiene Hypothesis, 13. Climate action, Female, MESH: Female
Abstract: International audience; The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19−induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome’s influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.
Published: 2021
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28. Short Chain Fatty Acids – mechanisms and functional importance in the gut

Author: Martin-Gallausiaux, Camille, Marinelli, Ludovica, Blottiere, Herve, Larraufie, Pierre, Lapaque, Nicolas, University of Luxembourg [Luxembourg], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914))
Subjects: digestive, oral, and skin physiology, gut 14, microbiota, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], SCFA, digestive system
Abstract: International audience; In recent years, the importance of the gut microbiota in human health has been revealed and many publications have highlighted its role as a key component of human physiology. Owing to the use of modern sequencing approaches, the characterisation of the microbiome in healthy individuals and in disease has demonstrated a disturbance of the microbiota, or dysbiosis, associated with pathological conditions. The microbiota establishes a symbiotic crosstalk with their host: commensal microbes benefit from the nutrient-rich environment provided by the gut and the microbiota produces hundreds of proteins and metabolites that modulate key functions of the host, including nutrient processing, maintenance of energy homoeostasis and immune system development. Many bacteria-derived metabolites originate from dietary sources. Among them, an important role has been attributed to the metabolites derived from the bacterial fermentation of dietary fibres, namely SCFA linking host nutrition to intestinal homoeostasis maintenance. SCFA are important fuels for intestinal epithelial cells (IEC) and regulate IEC functions through different mechanisms to modulate their proliferation, differentiation as well as functions of subpopulations such as enteroendocrine cells, to impact gut motility and to strengthen the gut barrier functions as well as host metabolism. Recent findings show that SCFA, and in particular butyrate, also have important intestinal and immuno-modulatory functions. In this review, we discuss the mechanisms and the impact of SCFA on gut functions and host immunity and consequently on human health.
Published: 2021

29. Alterations in Gut Microbiome in Cirrhosis as Assessed by Quantitative Metagenomics: Relationship With Acute-on-Chronic Liver Failure and Prognosis

Author: P. Huelin, Stanislav Dusko Ehrlich, K. J. D. e Silva, Isabel Graupera, Emmanuelle Le-Chatelier, Elsa Solà, Rebeca Moreira, Marta Carol, Cristina Solé, Magali Berland, Marta Llopis, Susie Guilly, Natalia Borruel, Gloria de Prada, Joël Doré, Elisa Pose, David Toapanta, Laura Napoleone, Francesc Casellas, Francisco Guarner, Adrià Juanola, Núria Fabrellas, Pere Ginès, Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Barcelona, Vall d'Hebron University Hospital [Barcelona], Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, project reference PI 12/00330 and PI 16/00043, ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), and European Project: 731875 ,LIVERHOPE
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Cirrosi hepàtica, Microbiota intestinal, Disease, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Model for End-Stage Liver Disease, Internal medicine, medicine, Humans, Prospective Studies, KEGG, Hepatic encephalopathy, Gastrointestinal microbiome, Aged, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Hepatology, business.industry, Liver failure, Acute-On-Chronic Liver Failure, Middle Aged, medicine.disease, Prognosis, Gut microbiome, 3. Good health, Gastrointestinal Microbiome, Survival Rate, 030104 developmental biology, Hepatic cirrhosis, Metagenomics, Case-Control Studies, 030211 gastroenterology & hepatology, Female, Insuficiència hepàtica, business
Abstract: Background and Aims Cirrhosis is associated with changes in gut microbiome composition. Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. We investigated the gut microbiome in patients with cirrhosis encompassing the whole spectrum of disease (compensated, acutely decompensated without ACLF, and ACLF). A group of healthy subjects was used as control subjects. Methods Stool samples were collected prospectively in 182 patients with cirrhosis. DNA library construction and sequencing were performed using the Ion Proton Sequencer (ThermoFisher Scientific, Waltham, MA). Microbial genes were grouped into clusters, denoted as metagenomic species. Results Cirrhosis was associated with a remarkable reduction in gene and metagenomic species richness compared with healthy subjects. This loss of richness correlated with disease stages and was particularly marked in patients with ACLF and persisted after adjustment for antibiotic therapy. ACLF was associated with a significant increase of Enterococcus and Peptostreptococcus sp and a reduction of some autochthonous bacteria. Gut microbiome alterations correlated with model for end-stage liver disease and Child-Pugh scores and organ failure and was associated with some complications, particularly hepatic encephalopathy and infections. Interestingly, gut microbiome predicted 3-month survival with good stable predictors. Functional analysis showed that patients with cirrhosis had enriched pathways related to ethanol production, γ-aminobutyric acid metabolism, and endotoxin biosynthesis, among others. Conclusions Cirrhosis is characterized by marked alterations in gut microbiome that parallel disease stages with maximal changes in ACLF. Altered gut microbiome was associated with complications of cirrhosis and survival. Gut microbiome may contribute to disease progression and poor prognosis. These results should be confirmed in future studies.
Published: 2021
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30. Fecal microbiota transplant from human to mice gives insights into the role of the gut microbiota in non-alcoholic fatty liver disease (NAFLD)

Author: Burz, Sebastian D., Monnoye, Magali, Philippe, Catherine, Farin, William, Ratziu, Vlad, Strozzi, Francesco, Paillarse, Jean-Michel, Chêne, Laurent, Blottière, Hervé M., Gérard, Philippe, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Enterome, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: high-fat diet, lcsh:Biology (General), NAFL, NAFLD, [SDV]Life Sciences [q-bio], gut microbiome, health, human, liver, lcsh:QH301-705.5, digestive system, Article, high-fructose
Abstract: International audience; Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol thanmice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.
Published: 2021

31. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author: Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. -L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Berrettini, W. H., Boehm, I., Boni, C., Boraska Perica, V., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Gratacos Mayora, M., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Grove, J., Henders, A. K., Larsen, J. T., Parker, R., Petersen, L. V., Jordan, J., Kennedy, M. A., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Mortensen, P. B., Polimanti, R., Mcclintick, J. N., Adkins, A. E., Aliev, F., Bacanu, S. -A., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L. -S., Clarke, T. -K., Degenhardt, F., Docherty, A. R., Edwards, A. C., Foo, J. C., Fox, L., Frank, J., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Hodgkinson, C., Hoffmann, P., Hottenga, J. -J., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., Mcintosh, A. M., Mcqueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Peterson, R. E., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J. -C., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., Zhou, H., Boardman, J. D., Chen, D., Choi, D. -S., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Frye, M. A., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S. H., Wodarz, N., Zill, P., Adkins, D. E., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Costello, E. J., de Wit, H., Diazgranados, N., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Iacono, W. G., Johnson, E. O., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lind, P. A., Mcgue, M., Mackillop, J., Madden, P. A. F., Maes, H. H., Magnusson, P. K. E., Nelson, E. C., Nothen, M. M., Palmer, A. A., Penninx, B. W. J. H., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R. J., Shen, P. -H., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Wade, T. D., Heath, A. C., Montgomery, G. W., Martin, N. G., Sullivan, P. F., Kaprio, J., Breen, G., Gelernter, J., Edenberg, H. J., Bulik, C. M., and Agrawal, A.
Subjects: Netherlands Twin Register (NTR), Alcoholism/genetics, Schizophrenia/genetics, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Medicine (miscellaneous), Genome-wide association study, Alcohol use disorder, Anorexia nervosa, Linkage Disequilibrium, ddc:616.89, [SCCO]Cognitive science, 0302 clinical medicine, Risk Factors, Tobacco Use Disorder/genetics, Substance-Related Disorders/genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Factors de risc en les malalties, Bulimia nervosa, Feeding and Eating Disorders/genetics, eating disorders, genetic correlation, substance use, Tobacco Use Disorder, 3. Good health, Fenotip, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Alcoholism, Eating disorders, Phenotype, Schizophrenia, Drinking of alcoholic beverages, eating disorder, Consum d'alcohol, Major depressive disorder, medicine.symptom, Depressive Disorder, Major/genetics, eating disorders, genetic correlation, substance use, Clinical psychology, Substance abuse, Risk factors in diseases, Substance-Related Disorders, Polymorphism, Single Nucleotide, Article, Feeding and Eating Disorders, 03 medical and health sciences, SDG 3 - Good Health and Well-being, mental disorders, Genetics, medicine, Humans, Trastorns de la conducta alimentària, 030304 developmental biology, Genetic association, Pharmacology, Depressive Disorder, Major, Binge eating, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SCCO] Cognitive science, medicine.disease, Comorbidity, Twin study, 030227 psychiatry, Abús de substàncies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Genètica, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract: Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs
Published: 2021

32. Modern Metaproteomics: A Unique Tool to Characterize the Active Microbiome in Health and Diseases, and Pave the Road towards New Biomarkers—Example of Crohn’s Disease and Ulcerative Colitis Flare-Ups

Author: Céline Henry, Ariane Bassignani, Magali Berland, Olivier Langella, Harry Sokol, Catherine Juste, Sokol, Harry, Plateforme d'Analyse Protéomique de Paris Sud Ouest (PAPPSO), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Crohn’s disease, [SDV] Life Sciences [q-bio], Feces, Crohn Disease, Microbiota, [SDV]Life Sciences [q-bio], Humans, biomarkers, Colitis, Ulcerative, metaproteomics, General Medicine, mass spectrometry, ulcerative colitis
Abstract: International audience; Thanks to the latest developments in mass spectrometry, software and standards, metaproteomics is emerging as the vital complement of metagenomics, to make headway in understanding the actual functioning of living and active microbial communities. Modern metaproteomics offers new possibilities in the area of clinical diagnosis. This is illustrated here, for the still highly challenging diagnosis of intestinal bowel diseases (IBDs). Using bottom-up proteomics, we analyzed the gut metaproteomes of the same twenty faecal specimens processed either fresh or after a two-month freezing period. We focused on metaproteomes of microbial cell envelopes since it is an outstanding way of capturing host and host–microbe interaction signals. The protein profiles of pairs of fresh and frozen-thawed samples were closely related, making feasible deferred analysis in a distant diagnosis centre. The taxonomic and functional landscape of microbes in diverse IBD phenotypes—active ulcerative colitis, or active Crohn’s disease either with ileo-colonic or exclusive colonic localization—differed from each other and from the controls. Based on their specific peptides, we could identify proteins that were either strictly overrepresented or underrepresented in all samples of one clinical group compared to all samples of another group, paving the road for promising additional diagnostic tool for IBDs.
Published: 2022

33. Integration of time-series meta-omics data reveals how microbial ecosystems respond to disturbance

Author: James M. Schupp, Emilie E. L. Muller, Christian Jäger, Paul Keim, Laura Lebrun, Haixu Tang, Malte Herold, Paul Wilmes, Hugo Roume, Sujun Li, Michael R. Hoopmann, John D. Gillece, Patrick May, Abdul Sheik, Benoit J. Kunath, Luise A. K. Kleine-Borgmann, Irina Bessarab, Cedric Christian Laczny, Susana Martinez Arbas, Rohan Benjamin Hugh Williams, Yuzhen Ye, Anna Heintz-Buschart, Robert L. Moritz, Shaman Narayanasamy, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique moléculaire, génomique, microbiologie (GMGM), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Water microbiology, Proteomics, 0301 basic medicine, meta-metabolomics, Microbiologie [F11] [Sciences du vivant], Time Factors, General Physics and Astronomy, Wastewater, Microbial ecology, Bioreactors, Dynamical systems, activated sludge, Microbiology [F11] [Life sciences], lcsh:Science, ComputingMilieux_MISCELLANEOUS, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, metatranscriptomics, Multidisciplinary, Microbiota, Community structure, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 6. Clean water, metaproteomics, Science, 030106 microbiology, Niche, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Metabolomics, ecological niche, wastewater, Ecosystem, Ecological niche, metagenomics, Phenotypic plasticity, Bacteria, Resistance (ecology), General Chemistry, 15. Life on land, 030104 developmental biology, 13. Climate action, Evolutionary biology, Metagenomics, Metaproteomics, Metagenome, lcsh:Q, lipid accumulating organisms, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, time series, Adaptation
Abstract: The development of reliable, mixed-culture biotechnological processes hinges on understanding how microbial ecosystems respond to disturbances. Here we reveal extensive phenotypic plasticity and niche complementarity in oleaginous microbial populations from a biological wastewater treatment plant. We perform meta-omics analyses (metagenomics, metatranscriptomics, metaproteomics and metabolomics) on in situ samples over 14 months at weekly intervals. Based on 1,364 de novo metagenome-assembled genomes, we uncover four distinct fundamental niche types. Throughout the time-series, we observe a major, transient shift in community structure, coinciding with substrate availability changes. Functional omics data reveals extensive variation in gene expression and substrate usage amongst community members. Ex situ bioreactor experiments confirm that responses occur within five hours of a pulse disturbance, demonstrating rapid adaptation by specific populations. Our results show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity, and set the foundation for future ecological engineering efforts., Herold et al. present an integrated meta-omics framework to investigate how mixed microbial communities, such as oleaginous bacterial populations in biological wastewater treatment plants, respond with distinct adaptation strategies to disturbances. They show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity.
Published: 2020

34. Investigating host-microbiome interactions by droplet based microfluidics

Author: Nicolas Terrapon, Liisa D. Van Vliet, Sandrine Laguerre, Elisabeth Laville, Joël Doré, Marion Leclerc, Pierre-Yves Colin, Bernard Henrissat, Jérémy Esque, Alexandra S. Tauzin, Florian Hollfelder, Mariana Rangel Pereira, Vincent Lombard, Gabrielle Potocki-Véronèse, Potocki-Veronese, Gabrielle [0000-0003-4232-230X], Apollo - University of Cambridge Repository, Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Cambridge [UK] (CAM), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Fundação) = CAPES Foundation [Brasilia] (CAPES), Drop-Tech Ltd., Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), KingAbdulaziz University, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Royal Society Newton fellowship, CAPES, European Project: 707457,H2020,H2020-MSCA-IF-2015,CaTSYS(2016), European Project: 685474,H2020,H2020-LEIT-BIO-2015-1,METAFLUIDICS(2016), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Microbiology (medical), Male, Glycan, [SDV]Life Sciences [q-bio], Microfluidics, Context (language use), Computational biology, Bacterial genome size, Biology, Microbiology, Beta-N-acetylgalactosaminidase, lcsh:Microbial ecology, 03 medical and health sciences, Human glycans, Humans, Genomic library, Microbiome, 030304 developmental biology, Droplet microfluidics, 0303 health sciences, Bacteria, Host Microbial Interactions, 030306 microbiology, Research, Microbiota, Middle Aged, Fosmid, Beta-N-acetyl-galactosaminidase, Metagenomics, Beta-N-Acetyl-Galactosaminidase, biology.protein, lcsh:QR100-130, Functional metagenomics, Human gut microbiota
Abstract: Funder: Royal Society Newton fellowship, Funder: CAPES Scholarship - Brazil, Background: Despite the importance of the mucosal interface between microbiota and the host in gut homeostasis, little is known about the mechanisms of bacterial gut colonization, involving foraging for glycans produced by epithelial cells. The slow pace of progress toward understanding the underlying molecular mechanisms is largely due to the lack of efficient discovery tools, especially those targeting the uncultured fraction of the microbiota. Results: Here, we introduce an ultra-high-throughput metagenomic approach based on droplet microfluidics, to screen fosmid libraries. Thousands of bacterial genomes can be covered in 1 h of work, with less than ten micrograms of substrate. Applied to the screening of the mucosal microbiota for β-N-acetylgalactosaminidase activity, this approach allowed the identification of pathways involved in the degradation of human gangliosides and milk oligosaccharides, the structural homologs of intestinal mucin glycans. These pathways, whose prevalence is associated with inflammatory bowel diseases, could be the result of horizontal gene transfers with Bacteroides species. Such pathways represent novel targets to study the microbiota-host interactions in the context of inflammatory bowel diseases, in which the integrity of the mucosal barrier is impaired. Conclusion: By compartmentalizing experiments inside microfluidic droplets, this method speeds up and miniaturizes by several orders of magnitude the screening process compared to conventional approaches, to capture entire metabolic pathways from metagenomic libraries. The method is compatible with all types of (meta)genomic libraries, and employs a commercially available flow cytometer instead of a custom-made sorting system to detect intracellular or extracellular enzyme activities. This versatile and generic workflow will accelerate experimental exploration campaigns in functional metagenomics and holobiomics studies, to further decipher host-microbiota relationships. BEyZgKg3YsWtKJ_ei8gXkiVideo Abstract
Published: 2020

35. Impact of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy on gut microbiota: a metagenomic comparative analysis

Author: Christophe Bonny, Frédéric Magoulès, William Farin, Nicolas Pons, Florian Plaza Oñate, Bettina Woelnerhanssen, David Nocca, Christoph Beglinger, Alessandra C. L. Cervino, S. Dusko Ehrlich, Jonathan Plassais, Enterome, Université Paris-Saclay, Department of Biomedicine [Basel], University Hospital Basel [Basel], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de chirurgie digestive, [CHU Montpellier], CentraleSupélec, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre for Host-Microbiome Interactions, Dental Institute Central Office, and King‘s College London
Subjects: medicine.medical_specialty, Sleeve gastrectomy, medicine.medical_treatment, Gastric Bypass, Veillonella, 030209 endocrinology & metabolism, Gut flora, Laparoscopic Roux-en-Y gastric bypass, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Gastrectomy, Weight loss, Internal medicine, Humans, Medicine, Microbiome, Bariatric surgery, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, biology, business.industry, biology.organism_classification, Roux-en-Y anastomosis, Gastrointestinal Microbiome, Obesity, Morbid, 3. Good health, Surgery, Metagenomics, Laparoscopy, 030211 gastroenterology & hepatology, France, medicine.symptom, business, Switzerland, Akkermansia muciniphila
Abstract: Background: Bariatric surgery is an effective therapeutic procedure for morbidly obese patients. The 2 most common interventions are sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Objectives: The aim of this study was to compare microbiome long-term microbiome after SG and LRYGB surgery in obese patients. Methods: Eighty-nine and 108 patients who underwent SG and LRYGB, respectively, were recruited. Stools were collected before and 6 months after surgery. Microbial DNA was analyzed with shotgun meta-genomic sequencing (SOLiD 5500 xl Wildfire). MSPminer, a novel innovative tool to characterize new in silico biological entities, was used to identify 715 Metagenomic Species Pan-genome. One hundred forty-eight functional modules were analyzed using GOmixer and KEGG database. Results: Both interventions resulted in a similar increase of Shannon's diversity index and gene richness of gut microbiota, in parallel with weight loss, but the changes of microbial composition were different. LRYGB led to higher relative abundance of aero-tolerant bacteria, such as Escherichia coli and buccal species, such as Streptococcus and Veillonella spp. In contrast, anaerobes, such as Clostridium, were more abundant after SG, suggesting better conservation of anaerobic conditions in the gut. Enrichment of Akkermansia muciniphila was also observed after both surgeries. Function-level changes included higher potential for bacterial use of supplements, such as vitamin B12, B1, and iron upon LRYGB. Conclusion: Microbiota changes after bariatric surgery depend on the nature of the intervention. LRYGB induces greater taxonomic and functional changes in gut microbiota than SG. Possible long-term health consequences of these alterations remain to be established. (Surg Obes Relat Dis 2020;16: 852-862.) Ó 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Published: 2020

36. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author: Hugo Roume, Gwen Falony, Jean-Daniel Zucker, Sothea Touch, Lars Køber, Sofia K. Forslund, Fabrizio Andreelli, Stanislav Dusko Ehrlich, Luis Pedro Coelho, Peer Bork, Jens Nielsen, Karen E. Assmann, Marc-Emmanuel Dumas, Thi Thuy Duyen Nguyen, Christine Rouault, Sara Vieira-Silva, Helle Krogh Pedersen, Torben Hansen, Eugeni Belda, Sebastian Proost, Nathalie Galleron, Mireia Valles-Colomer, Christian Lewinter, Trine Nielsen, Jens Peter Gøtze, Michael Stumvoll, Pilar Galan, Jean-Michel Oppert, Judith Aron-Wisnewsky, Jean-Sébastien Hulot, Ivica Letunic, Nadja B Søndertoft, Benoit Quinquis, Joe-Elie Salem, Karine Clément, Tue H. Hansen, Rima Chakaroun, Fredrik Bäckhed, Nicolas Pons, Jens J. Holst, Henrik Vestergaard, Edi Prifti, Jean-Phillippe Bastard, Jeroen Raes, Oluf Pedersen, Valentina Tremaroli, Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Dept Biol Struct, Flanders Institute for Biotechnology, Integromics [Paris], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Medical Department III – Endocrinology, Nephrology, Rheumatology, Universität Leipzig [Leipzig], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Université Catholique de Louvain (UCL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), VIB-KU Leuven Center for Microbiology [Leuven, Belgium], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), University of Gothenburg (GU), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Tenon [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fudan University [Shanghai], CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Metabolism, Digestion and Reproduction, Imperial College London, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biobyte Solution, Department of Biology and Biological Engineering, Chalmers University of Technology, Chalmers University of Technology [Gothenburg, Sweden], European Molecular Biology Laboratory (EMBL), University of Heidelberg, Medical Faculty, University of Würzburg, Wallenberg Laboratory, Göteborgs Universitet (GU), The promotor of the clinical study was the Assistance Publique Hôpitaux de Paris (APHP). S.V.-S. was supported by a post-doctoral fellowship from the Research Foundation Flanders (FWO Vlaanderen). The Raes laboratory is supported by the VIB Grand Challenges programme, KU Leuven, the Rega Institute for Medical Research, and the FWO EOS program (30770923). The Novo Nordisk Foundation Center for Basic Metabolic Research., ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], LE CHATELIER, Emmanuelle, Démonstrateurs - MetaGenoPolis - - MGP2011 - ANR-11-DPBS-0001 - DPBS - VALID, Instituts Hospitalo-Universitaires - Institut de Cardiologie-Métabolisme-Nutrition - - ICAN2010 - ANR-10-IAHU-0005 - IAHU - VALID, Metagenomics in Cardiometabolic Diseases - METACARDIS - - EC:FP7:HEALTH2012-11-01 - 2017-10-31 - 305312 - VALID, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), VIB-KU Leuven Center for Microbiology [Belgium], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Service de diabétologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC Paris Est, Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: 0301 basic medicine, Male, Feces/microbiology, [SDV]Life Sciences [q-bio], Overweight, Gut flora, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Cohort Studies, Feces, 0302 clinical medicine, Prevalence, Medicine, Bacteroides, Gastrointestinal Microbiome/drug effects, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, education.field_of_study, Multidisciplinary, biology, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Enterotype, Female, medicine.symptom, Inflammatory Bowel Diseases/microbiology, Obesity/microbiology, medicine.medical_specialty, Bacteroides/isolation & purification, Population, 03 medical and health sciences, Internal medicine, Humans, Microbiome, Obesity, education, Faecalibacterium, business.industry, medicine.disease, biology.organism_classification, Inflammatory Bowel Diseases, Gastrointestinal Microbiome, MetaCardis Consortium, Dysbiosis/epidemiology, 030104 developmental biology, Cross-Sectional Studies, Dysbiosis, Faecalibacterium/isolation & purification, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Body mass index
Abstract: Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.
Published: 2020

37. Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management

Author: Manon Dominique, Nicolas Lucas, Charlène Guérin, Pierre Déchelotte, Jean-Claude do Rego, Romain Legrand, Fatima Léon, Julie Rondeaux, Camille Deroissart, Grégory Lambert, S. Nobis, Saïda Azhar, Marie-Anne Le Solliec, Sergueï O. Fetissov, Nicolas Pons, S. Dusko Ehrlich, TargEDys SA Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Service Commun d'Analyse Comportementale (SCAC), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Service de nutrition [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), TargEDys Rouen, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaGenoPolis (MGP (US 1367)), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Appetite, Mice, Obese, Medicine (miscellaneous), Adipose tissue, 030209 endocrinology & metabolism, Biology, Overweight, Article, law.invention, Eating, Mice, 03 medical and health sciences, Probiotic, 0302 clinical medicine, law, Internal medicine, medicine, Animals, Obesity, ComputingMilieux_MISCELLANEOUS, media_common, 2. Zero hunger, Meal, Nutrition and Dietetics, Bacteria, Probiotics, Body Weight, Hafnia alvei, medicine.disease, Gastrointestinal Microbiome, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Adipose Tissue, medicine.symptom, CLPB, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Hormone
Abstract: Background/objectives Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. Methods The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the “MetaHIT” database. Results Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p p ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p ob/ob mice (p H.alvei -treated ob/ob mice (p Enterobacter, Klebsiella and Hafnia. Conclusions H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.
Published: 2020

38. Comparative methods for fecal sample storage to preserve gut microbial structure and function in an in vitro model of the human colon

Author: Muriel Thomas, Cécile Verdier, Charlotte Deschamps, Monique Alric, Sophie Comtet-Marre, Stéphanie Blanquet-Diot, Mathieu Almeida, Elora Fournier, Nathalie Kapel, Lucie Etienne-Mesmin, Ophélie Uriot, Claire Cherbuy, Frédérique Lajoie, Microbiologie Environnement Digestif Santé (MEDIS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Montréal (UdeM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Coprologie Fonctionnelle [Pitié-Salpêtrière], Sorbonne Université (SU), Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by fellowships from Ministère de laRecherche (France) to F. E. and MITACS (Canada) to L. F., OBFIBRESCUSI grant from Auvergne Rhone Alpes Region to D.C. and PSPC-BpiFrance RESTORBIOME funding for consumables.Ministry of Research, France MITACS (Canada) OBFIBRE SCUSI grant from Auvergne Rhone Alpes Region PSPC-Bpi France RESTORBIOME, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Preservative, Cryoprotectant, Colon, [SDV]Life Sciences [q-bio], Applied Microbiology and Biotechnology, Specimen Handling, 03 medical and health sciences, chemistry.chemical_compound, Feces, In vivo, RNA, Ribosomal, 16S, Glycerol, Humans, Food science, In vitro M-ARCOL model, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Fecal sample, Human microbiome, General Medicine, Trehalose, Gastrointestinal Microbiome, chemistry, Preservation method, Fermentation, Human gut microbiota, Biotechnology
Abstract: International audience; In vitro gut models, such as the mucosal artificial colon (M-ARCOL), provide timely and cost-efficient alternatives to in vivo assays allowing mechanistic studies to better understand the role of human microbiome in health and disease. Using such models inoculated with human fecal samples may require a critical step of stool storage. The effects of preservation methods on microbial structure and function in in vitro gut models have been poorly investigated. This study aimed to assess the impact of three commonly used preserving methods, compared with fresh fecal samples used as a control, on the kinetics of lumen and mucus-associated microbiota colonization in the M-ARCOL model. Feces from two healthy donors were frozen 48 h at − 80°C with or without cryoprotectant (10% glycerol) or lyophilized with maltodextrin and trehalose prior to inoculation of four parallel bioreactors (e.g., fresh stool, raw stool stored at − 80°C, stool stored at − 80°C with glycerol and lyophilized stool). Microbiota composition and diversity (qPCR and 16S metabarcoding) as well as metabolic activity (gases and short chain fatty acids) were monitored throughout the fermentation process (9 days). All the preservative treatments allowed the maintaining inside the M-ARCOL of a complex and functional microbiota, but considering stabilization time of microbial profiles and activities (and not technical constraints associated with the supply of frozen material), our results highlighted 48 h freezing at − 80°C without cryoprotectant as the most efficient method. These results will help scientists to determine the most accurate method for fecal storage prior to inoculation of in vitro gut microbiome models. Key points • In vitro ARCOL model reproduces luminal and mucosal human microbiome. • Short-term storage of fecal sample influences microbial stabilization and activity. • 48 h freezing at − 80°C: most efficient method to preserve microbial ecosystem. • Scientific and technical requirements: influencers of preservation method.
Published: 2020

39. Introduction to host microbiome symbiosis in health and disease

Author: Béatrice Gaugler, Florent Malard, Mohamad Mohty, Joël Doré, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Research Council (ERC), European Project: 788191,Homo.symbiosus, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Ecology (disciplines), Immunology, Iatrogenic Disease, Computational biology, Disease, Review Article, Biology, 03 medical and health sciences, 0302 clinical medicine, Symbiosis, medicine, Immunology and Allergy, Animals, Humans, Microbiome, Precision Medicine, Host Microbial Interactions, Microbiota, Human microbiome, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, 030104 developmental biology, Metagenomics, Dysbiosis, Enterotype, Nutrition Therapy, 030215 immunology
Abstract: International audience; Humans share a core intestinal microbiome and yet human microbiome differs by genes, species, enterotypes (ecology), and gene count (microbial diversity). Achievement of microbiota metagenomic analysis has revealed that the microbiome gene count is a key stratifier of health in several immune disorders and clinical conditions. We review here the progress of the metagenomic pipeline analysis, and how this has allowed us to define the host–microbe symbiosis associated with a healthy status. The link between host–microbe symbiosis disruption, the so-called dysbiosis and chronic diseases or iatrogenic conditions is highlighted. Finally, opportunities to use microbiota modulation, with specific nutrients and/or live microbes, as a target for personalized nutrition and therapy for the maintenance, preservation, or restoration of host–microbe symbiosis are discussed.
Published: 2020

40. Impact of pemetrexed chemotherapy on the gut microbiota and intestinal inflammation of patient-lung-derived tumor xenograft (PDX) mouse models

Author: Hervé M. Blottière, Françoise Le Vacon, Cindy Pensec, Thomas Carton, Sébastien Leuillet, Mario Campone, Florence Gillaizeau, Anne Bessard, Michel Neunlist, Dominique Guenot, Biofortis Mérieux NutriSciences [Saint-Herblain], IMODI Consortium, Laboratory EA3430. Progression tumorale et microenvironnement, Approches Translationnelles et Epidémiologie, University of Strasbourg, 3 avenue Molière, 67000 Strasbourg, France, The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French National Research Agency (ANR) IMODI Consortium, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by an ANRT subvention (CIFRE fellowship) and the IMODI Consortium., and Bodescot, Myriam
Subjects: Lung Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, Mice, SCID, Gut flora, TOXICITY, Carcinoma, Non-Small-Cell Lung, Medicine, Intestinal Mucosa, lcsh:Science, 0303 health sciences, Multidisciplinary, biology, CANCER, 3. Good health, Specific Pathogen-Free Organisms, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pemetrexed, OBESITY, Toxicity, BACTERIA, Heterografts, Female, medicine.symptom, medicine.drug, Tumor Graft, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Inflammation, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, digestive system, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Carcinoma, Animals, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Chemotherapy, Intestinal permeability, 030306 microbiology, business.industry, lcsh:R, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Disease Models, Animal, Cancer research, FECAL MICROBIOTA, lcsh:Q, Metagenomics, business, Non-small-cell lung cancer, Neoplasm Transplantation
Abstract: Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota’s role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown. The objective of this study was to evaluate the impact of pemetrexed and the tumor graft on the gut microbiota composition in immunodeficient mice. The faecal microbiota composition was studied with metabarcoding before, 24-h and one week after treatment. The colon epithelial barrier integrity was evaluated by histological examination, intestinal permeability measurement, and selected cytokines quantification. The tumor graft induced some variations in the microbiota composition. Pemetrexed further increased the relative abundance of Enterobacteriaceae and 3 families from the Firmicutes phylum: Enterococcaceae, Lactobacillaceae and Streptococcaceae. Pemetrexed also significantly altered the epithelial barrier integrity, which was associated with early inflammation. This pilot study shows that the association of a lung tumor graft with pemetrexed causes an alteration in the microbiota composition. Such information increases our knowledge about the impact of chemotherapy on the microbiota, which could help to minimize side effects and improve therapeutic effectiveness in the future.
Published: 2020

41. Gut Microbiota Profile of Obese Diabetic Women Submitted to Roux-en-Y Gastric Bypass and Its Association with Food Intake and Postoperative Diabetes Remission

Author: Karina Al Assal, Jean-Daniel Zucker, B.D. Balmant, João C. Setubal, Priscila Sala, Andrew Maltez Thomas, Carla R. Taddei, Dan Linetzky Waitzberg, Danielle Cristina Fonseca, Florence Levenez, Marco Aurelio Santo, Emmanuel Dias-Neto, Karine Clément, Maria Carlota Dao, G. Belarmino, Joël Doré, Edi Prifti, Raquel Susana Torrinhas, Ilanna Marques Gomes da Rocha, Eugeni Belda, University of São Paulo (USP), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Pitié BT, Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Biocomplexity Institute of Virginia Tech [Blacksburg], Virginia Tech [Blacksburg], European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Universidade de São Paulo = University of São Paulo (USP), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Gestionnaire, Hal Sorbonne Université, and Metagenomics in Cardiometabolic Diseases - METACARDIS - - EC:FP7:HEALTH2012-11-01 - 2017-10-31 - 305312 - VALID
Subjects: 0301 basic medicine, type 2 diabetes mellitus, Type 2 diabetes, Gut flora, Gastroenterology, Eating, 0302 clinical medicine, RNA, Ribosomal, 16S, Postoperative Period, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Nutrition and Dietetics, biology, digestive, oral, and skin physiology, Remission Induction, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Roux-en-Y anastomosis, Obesity, Morbid, Treatment Outcome, Female, lcsh:Nutrition. Foods and food supply, Adult, medicine.medical_specialty, Firmicutes, bariatric surgery, Gastric Bypass, 030209 endocrinology & metabolism, lcsh:TX341-641, digestive system, Article, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Humans, Receiver operating characteristic, gut microbiota, business.industry, nutritional and metabolic diseases, Bacteroidetes, Type 2 Diabetes Mellitus, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, Diabetes Mellitus, Type 2, BIOTA INTESTINAL, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: Gut microbiota composition is influenced by environmental factors and has been shown to impact body metabolism. Objective: To assess the gut microbiota profile before and after Roux-en-Y gastric bypass (RYGB) and the correlation with food intake and postoperative type 2 diabetes remission (T2Dr). Design: Gut microbiota profile from obese diabetic women was evaluated before (n = 25) and 3 (n = 20) and 12 months (n = 14) after RYGB, using MiSeq Illumina-based V4 bacterial 16S rRNA gene profiling. Data on food intake (7-day record) and T2Dr (American Diabetes Association (ADA) criteria) were recorded. Results: Preoperatively, the abundance of five bacteria genera differed between patients with (57%) and without T2Dr (p &lt, 0.050). Preoperative gut bacteria genus signature was able to predict the T2Dr status with 0.94 accuracy ROC curve (receiver operating characteristic curve). Postoperatively (vs. preoperative), the relative abundance of some gut bacteria genera changed, the gut microbial richness increased, and the Firmicutes to Bacteroidetes ratio (rFB) decreased (p &lt, 0.05) regardless of T2Dr. Richness levels was correlated with dietary profile pre and postoperatively, mainly displaying positive and inverse correlations with fiber and lipid intakes, respectively (p &lt, 0.05). Conclusions: Gut microbiota profile was influenced by RYGB and correlated with diet and T2Dr preoperatively, suggesting the possibility to assess its composition to predict postoperative T2Dr.
Published: 2020

42. Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients

Author: Conrad Rauber, Gladys Ferrere, Jean-Eudes Fahrner, Valerio Iebba, Nicolas Pons, Romain Daillère, Emmanuelle Le Chatellier, Hugo Roume, Filippo Pietrantonio, Nicola Segata, Marine Fidelle, Anne-Gaëlle Goubet, Carolina Alves Costa Silva, Bertrand Routy, Connie P.M. Duong, Karim Fizazi, Edoardo Pasolli, Safae Terrisse, Beatrice Casu, Laurence Albiges, Bernard Escudier, Mélodie Bonvalet, Maryam Tidjani Alou, Laurie Alla, Kristina Iribarren, Didier Raoult, Aude Desnoyer, Guido Kroemer, Lisa Derosa, Laura Mondragón, Nathalie Galleron, Anna Reni, Fabien Lemaitre, Laurence Zitvogel, Derosa, L., Routy, B., Fidelle, M., Iebba, V., Alla, L., Pasolli, E., Segata, N., Desnoyer, A., Pietrantonio, F., Ferrere, G., Fahrner, J. -E., Le Chatellier, E., Pons, N., Galleron, N., Roume, H., Duong, C. P. M., Mondragon, L., Iribarren, K., Bonvalet, M., Terrisse, S., Rauber, C., Goubet, A. -G., Daillere, R., Lemaitre, F., Reni, A., Casu, B., Alou, M. T., Alves Costa Silva, C., Raoult, D., Fizazi, K., Escudier, B., Kroemer, G., Albiges, L., Zitvogel, L., Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Faculté de médecine de l'Université Paris-Sud [Kremlin Bicêtre, Paris], Université Paris-Saclay, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Naples Federico II = Università degli studi di Napoli Federico II, Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), IRCCS Istituto Nazionale dei Tumori [Milano], Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Suzhou Institute of Systems Medicine [Jiangsu, P.R. China], Karolinska University Hospital [Stockholm], Philanthropia Foundation ESMO translational research fellowship Fonds de la Recherche en Sante du Quebec Kidney Cancer Research Network of Canada Ligue nationale contre le cancerFrench National Research Agency (ANR)French National Research Agency (ANR)ERA-Net for Research on Rare Diseases Fondation ARC pour la Recherche sur le CancerRegion Ile-de-France Fondation de FranceFondation pour la Recherche MedicaleEuropean Commission Joint Research CentreEuropean Research Council (ERC)Fondation Carrefour, High-end Foreign Expert Program in China GDW20171100085 GDW20181100051Institut National du Cancer (INCA) FranceInserm (HTE) Institut Universitaire de France Leducq FoundationSearave and Carrefour Foundation SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE 2.0) BMS Foundation SIRIC Cancer Research and Personalized Medicine (CARPEM) Paris Alliance of Cancer Research Institutes (PACRI) Mediterranee Infection 10-IAHU-03Region Provence-Alpes-Cote d'AzurNational Research, Development and Innovation Fund of Hungary FIEK_16-1-20160005Research and Technology Innovation Fund NAP2-2017-1.2.1-NKP-0002Breast Cancer Research Foundation BCRF-17-156Novo Nordisk Foundation Interdisciplinary Synergy Program Grant NNF15OC0016584, ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, University of Naples Federico II, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Gustave Roussy Cancer Campus (GRCC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Saclay, Université Paris-Sud [Le Kremlin-Bicêtre] (Faculté de Médecine), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre d’Investigation Clinique en Biothérapies [CHU Pitié-Salpêtrière] (CIC-BT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Paris-Saclay, Faculté de Pharmacie, 92290 Châtenay-Malabry, France, MetaGenoPolis, European Institute of Oncology [Milan] (ESMO), Gustave Roussy Cancer Campus, Partenaires INRAE, Chinese Academy of Medical Sciences, Philanthropia Foundation ESMO translational research fellowship.Fonds de la Recherche en Sante du Quebec Kidney Cancer Research Network of CanadaLigue nationale contre le cancerFrench National Research Agency (ANR) ERA-Net for Research on Rare DiseasesFondation ARC pour la Recherche sur le CancerRegion Ile-de-FranceFondation de FranceFondation pour la Recherche MedicaleEuropean Commission Joint ResearchCentre European Research Council (ERC)Fondation Carrefour, and High-end Foreign Expert Program in China GDW20171100085 GDW20181100051Institut National du Cancer (INCA) France Inserm (HTE) Institut Universitaire de FranceLeducq FoundationSearave and Carrefour Foundation SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE 2.0) BMS Foundation SIRIC Cancer Research and Personalized Medicine (CARPEM) Paris Alliance of Cancer Research Institutes (PACRI)Mediterranee Infection 10-IAHU-03Region Provence-Alpes-Cote d'AzurNational Research, Development and Innovation Fund of Hungary FIEK_16-1-20160005Research and Technology Innovation Fund NAP2-2017-1.2.1-NKP-0002Breast Cancer Research Foundation BCRF-17-156Novo Nordisk Foundation Interdisciplinary Synergy Program Grant NNF15OC0016584
Subjects: Oncology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Antibiotics, 030232 urology & nephrology, Tyrosine kinase inhibitor, Immune checkpoint inhibitor, Tyrosine-kinase inhibitor, Feces, Mice, 0302 clinical medicine, Cancer immunotherapy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Renal cell carcinoma, Prospective Studies, Immune Checkpoint Inhibitors, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiota, Kidney cancer, Kidney Neoplasms, 3. Good health, Nivolumab, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine.medical_specialty, medicine.drug_class, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Internal medicine, medicine, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Carcinoma, Renal Cell, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, business.industry, Antibiotic, Immunotherapy, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immune checkpoint, Gastrointestinal Microbiome, Drug Resistance, Neoplasm, business
Abstract: Background: The development of immune checkpoint blockade (ICB) has revolutionized the clinical outcome of renal cell carcinoma (RCC). Nevertheless, improvement of durability and prediction of responses remain unmet medical needs. While it has been recognized that antibiotics (ATBs) decrease the clinical activity of ICB across various malignancies, little is known about the direct impact of distinct intestinal nonpathogenic bacteria (commensals) on therapeutic outcomes of ICB in RCC. Objective: To evaluate the predictive value of stool bacteria composition for ICB efficacy in a cohort of advanced RCC patients. Design, setting, and participants: We prospectively collected fecal samples from 69 advanced RCC patients treated with nivolumab and enrolled in the GETUG-AFU 26 NIVOREN microbiota translational substudy phase 2 trial (NCT03013335) at Gustave Roussy. We recorded patient characteristics including ATB use, prior systemic therapies, and response criteria. We analyzed 2994 samples of feces from healthy volunteers (HVs). In parallel, preclinical studies performed in RCC-bearing mice that received fecal transplant (FMT) from RCC patients resistant to ICB (NR-FMT) allowed us to draw a cause-effect relationship between gut bacteria composition and clinical outcomes for ICB. The influence of tyrosine kinase inhibitors (TKIs) taken before starting nivolumab on the microbiota composition has also been assessed. Outcome measurements and statistical analysis: Metagenomic data (MG) from whole genome sequencing (WGS) were analyzed by multivariate and pairwise comparisons/fold ratio to identify bacterial fingerprints related to ATB or prior TKI exposure and patients’ therapeutic response (overall response and progression-free survival), and compared with the data from cancer-free donors. Results and limitations: Recent ATB use (n = 11; 16%) reduced objective response rates (from 28% to 9%, p < 0.03) and markedly affected the composition of the microbiota, facilitating the dominance of distinct species such as Clostridium hathewayi, which were also preferentially over-represented in stools from RCC patients compared with HVs. Importantly, TKIs taken prior to nivolumab had implications in shifting the microbiota composition. To establish a cause-effect relationship between gut bacteria composition and ICB efficacy, NR-FMT mice were successfully compensated with either FMT from responding RCC patients or beneficial commensals identified by WGS-MG (Akkermansia muciniphila and Bacteroides salyersiae). Conclusions: The composition of the microbiota is influenced by TKIs and ATBs, and impacts the success of immunotherapy. Future studies will help sharpen the role of these specific bacteria and their potential as new biomarkers. Patient summary: We used quantitative shotgun DNA sequencing of fecal microbes as well as preclinical models of fecal or bacterial transfer to study the association between stool composition and (pre)clinical outcome to immune checkpoint blockade. Novel insights into the pathophysiological relevance of intestinal dysbiosis in the prognosis of kidney cancer may lead to innovative therapeutic solutions, such as supplementation with probiotics to prevent primary resistance to therapy. Antibiotics prior to immune checkpoint inhibitors have a deleterious clinical impact, reduce the microbiome diversity, and increase Clostridium hathewayi bacteria associated with resistance. Higher baseline microbiome diversity and Akkermansia muciniphila are associated with longer progression-free survival. In murine fecal microbiome transplantation experiments, A. muciniphila can restore the anticancer activity of the combination of anti–PD-1 and CTLA-4.
Published: 2020

43. Microbiome definition re-visited : old concepts and new challenges

Author: Gema Herrero Corral, Rafael Soares Correa de Souza, Kellye Eversole, Joseph Selvin, Aaron M. Walsh, Michael Schloter, Gabriele Berg, G. Seghal Kiran, James Macklin, Luca Simone Cocolin, Michael Wagner, Tomislav Cernava, Xiaoyulong Chen, Angela Sessitsch, Doreen Fischer, Daria Rybakova, Nelson Lima, M.J. Ryan, Brajesh K. Singh, Linda L. Kinkel, Emmanuelle Maguin, Alexander Loy, Lene Lange, Leo van Overbeek, Tim H. Mauchline, Bettina Schelkle, Hugo Roume, Maria Kazou, Hauke Smidt, Birgit Mitter, Marie Christine Champomier Vergès, Ryan McClure, Inga Sarand, Trevor C. Charles, Graz University of Technology [Graz] (TU Graz), Helmholtz-Zentrum München (HZM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Waterloo [Waterloo], Metagenom Bio, Guizhou Medical University (贵州医科大学), Department of Agricultural, Forestry, and Food Sciences, University of Turin, International Alliance for Phytobiomes Research, Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agricultural University of Athens, University of Minnesota, St Paul, MN United States, Bioeconomy, Research and Advisory, University of Minho [Braga], University of Vienna [Vienna], Agriculture and Agri-Food [Ottawa] (AAFC), Rothamsted Research, Pacific Northwest National Laboratory (PNNL), Austrian Institute of Technology [Vienna] (AIT), CABI [Egham], Tallinn University of Technology (TTÜ), Wageningen University and Research [Wageningen] (WUR), EUFIC—European Food Information Council, MetaGenoPolis (MGP (US 1367)), Pondicherry University, Partenaires INRAE, Universidade Estadual de Campinas (UNICAMP), Western Sydney University, Teagasc Food Research Centre [Fermoy, Ireland], European Project: 818116,MicrobiomeSupport, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Agricultural, Forestry and Food Sciences, Università degli studi di Torino = University of Turin (UNITO), Département Microbiologie et Chaîne Alimentaire - INRAE (MICA), Agriculture and Agri-Food (AAFC), Biotechnology and Biological Sciences Research Council (BBSRC), Universidade Estadual de Campinas = University of Campinas (UNICAMP), European Project: 818116,H2020-SFS-2018-2020,MicrobiomeSupport (2018), European Union, Technische Universität Graz (TU Graz), Graz University of Technology, Department of Agricultural Forest and Food Sciences, Eversole Associates, Universidade do Minho, School of Integrative Plant Science, Cornell Univ., Department of Agrotechnology and Food Sciences [Wageningen], Wageningen University and Research Centre [Wageningen] (WUR), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Western Sydney University (UWS), SANOFI (Research and Development), Research and Development, Research Unit Comparative Microbiome Analysis (COMI), Microbiota Interaction with Human and Animal (MIHA), and Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute
Subjects: Microbiology (medical), Standardization, Best practice, [SDV]Life Sciences [q-bio], Biology, Microbiology, lcsh:Microbial ecology, Public interest, Biointeractions and Plant Health, 03 medical and health sciences, Surveys and Questionnaires, Terminology as Topic, Life Science, MolEco, Microbiome, Resilience (network), Set (psychology), Composition (language), VLAG, 030304 developmental biology, 0303 health sciences, Science & Technology, WIMEK, 030306 microbiology, Microbiota, Correction, PE&RC, Research findings, Data science, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Commentary, lcsh:QR100-130
Abstract: The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term ``microbiome.'' Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role., The study was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 818116 (Project MicrobiomeSupport)., info:eu-repo/semantics/publishedVersion
Published: 2020

44. Effects of Low-FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial

Author: Sébastien Fromentin, Samar B. Ibraim, James O. Lindsay, Nicolas Maziers, Kevin Whelan, Nathalie Galleron, Florence Levenez, Miranda Lomer, Peter M. Irving, Selina R Cox, Neil E. McCarthy, Andrew J. Stagg, Nicolas Pons, S. Dusko Ehrlich, Hugo Roume, Department of Nutritional Sciences, King‘s College London, Department of Gastroenterology, Barts Health NHS Trust, Royal Free Hospital [London, UK]-Royal Free Hospital [London, UK], Centre for Immunobiology, Blizard Institute, Queen Mary University of London (QMUL)-Queen Mary University of London (QMUL), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Nutrition and Dietetics, Guy's & St Thomas' NHS Foundation Trust, and Kenneth Rainin Foundation
Subjects: 0301 basic medicine, Male, Faecalibacterium prausnitzii, Disaccharides, Inflammatory bowel disease, Gastroenterology, Severity of Illness Index, Diet, Carbohydrate-Restricted, Feces, 0302 clinical medicine, UC, Single-Blind Method, Irritable bowel syndrome, 2. Zero hunger, Crohn's disease, biology, Monosaccharides, Middle Aged, Ulcerative colitis, 3. Good health, CD, Treatment Outcome, 030211 gastroenterology & hepatology, Female, HR-QOL, Adult, medicine.medical_specialty, 03 medical and health sciences, Young Adult, Internal medicine, IBS, medicine, Humans, Microbiome, Hepatology, Bacteria, business.industry, C-reactive protein, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, biology.organism_classification, Inflammatory Bowel Diseases, United Kingdom, Gastrointestinal Microbiome, 030104 developmental biology, biology.protein, Quality of Life, business, Biomarkers
Abstract: Background & Aims There is limited evidence that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) reduces gut symptoms in quiescent inflammatory bowel disease (IBD). We performed a randomized, controlled trial to investigate the effects of a low FODMAP diet on persistent gut symptoms, the intestinal microbiome, and circulating markers of inflammation in patients with quiescent IBD. Methods We performed a single-blind trial of 52 patients with quiescent Crohn's disease or ulcerative colitis and persistent gut symptoms at 2 large gastroenterology clinics in the United Kingdom. Patients were randomly assigned to groups that followed a diet low in FODMAPs (n = 27) or a control diet (n = 25), with dietary advice, for 4 weeks. Gut symptoms and health-related quality of life were measured using validated questionnaires. Stool and blood samples were collected at baseline and end of trial. We assessed fecal microbiome composition and function using shotgun metagenomic sequencing and phenotypes of T cells in blood using flow cytometry. Results A higher proportion of patients reported adequate relief of gut symptoms following the low FODMAP diet (14/27, 52%) than the control diet (4/25, 16%, P=.007). Patients had a greater reduction in irritable bowel syndrome severity scores following the low FODMAP diet (mean reduction of 67; standard error, 78) than the control diet (mean reduction of 34; standard error, 50), although this difference was not statistically significant (P = .075). Following the low FODMAP diet, patients had higher health-related quality of life scores (81.9 ± 1.2) than patients on the control diet (78.3 ± 1.2, P = .042). A targeted analysis revealed that in stool samples collected at the end of the study period, patients on the low FODMAP diet had significantly lower abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Faecalibacterium prausnitzii than patients on control diet. However, microbiome diversity and markers of inflammation did not differ significantly between groups. Conclusions In a trial of the low FODMAP diet vs a control diet in patients with quiescent IBD, we found no significant difference after 4 weeks in change in irritable bowel syndrome severity scores, but significant improvements in specific symptom scores and numbers reporting adequate symptom relief. The low FODMAP diet reduced fecal abundance of microbes believed to regulate the immune response, compared with the control diet, but had no significant effect on markers of inflammation. We conclude that a 4-week diet low in FODMAPs is safe and effective for managing persistent gut symptoms in patients with quiescent IBD. www.isrctn.com no.: ISRCTN17061468
Published: 2020

45. Late weaning is associated with increased microbial diversity and Faecalibacterium prausnitzii abundance in the fecal microbiota of piglets

Author: Massacci, Francesca Romana, Berri, Mustapha, Lemonnier, Gaetan, Guettier, Elodie, Blanc, Fany, Jardet, Deborah, Rossignol, Marie Noelle, Mercat, Marie-José, Doré, Joël, Lepage, Patricia, Rogel-Gaillard, Claire, Estellé, Jordi, Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Saclay (COmUE), Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche ‘Togo Rosati’, Partenaires INRAE, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Oiseaux et Aviculture (BOA), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Institut du Porc (IFIP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), FR Massacci received a PhD grant from the Department of Agricultural and Food Sciences (DISTAL), University of Bologna (Italy), ANR-14-CE18-0004,PIGLETBIOTA,PIGLETBIOTA : une étude de biologie intégrative de l'influence du microbiote intestinal sur la robustesse des porcelets au sevrage, dans la perspective de la réduction de l'usage des antibiotiques dans les élevages.(2014), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Recherche Agronomique (INRA)-Université de Tours
Subjects: Diversity, [SDV.GEN]Life Sciences [q-bio]/Genetics, lcsh:Veterinary medicine, Piglet, [SDV]Life Sciences [q-bio], lcsh:QR1-502, Weaning, Gut microbiota, lcsh:Microbiology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Age, F. Prausnitzii, fluids and secretions, lcsh:SF600-1100, [INFO]Computer Science [cs], Research Article
Abstract: International audience; Background: In pig production systems, weaning is a crucial period characterized by nutritional, environmental, and social stresses. Piglets transition from a milk-based diet to a solid, more complex plant-based diet, and their gut physiology must adapt accordingly. It is well established that piglets weaned later display improved health, better wean-to-finish growth performance, and lower mortality rates. The aim of this study was to evaluate the impact of weaning age on fecal microbiota diversity and composition in piglets. Forty-eight Large White piglets were divided into 4 groups of 12 animals that were weaned at different ages: 14 days (early weaning), 21 days (a common weaning age in intensive pig farming), 28 days (idem), and 42 days (late weaning). Microbiota composition was assessed in each group by sequencing the 16S rRNA gene using fecal samples taken on the day of weaning, 7 days later, and at 60 days of age. Results: In each group, there were significant differences in fecal microbiota composition before and after weaning (p < 0.05), confirming that weaning can drastically change the gut microbiota. Microbiota diversity was positively correlated with weaning ag e: microbial alpha diversity and richness were higher in piglets weaned at 42 days of age both on the day of weaning and 7 days later. The abundance of Faecalibacterium prausnitzii operational taxonomic units (OTUs) was also higher in piglets weaned at 42 days of age. Conclusions: Overall, these results show that late weaning increased gut microbiota diversity and the abundance of F. prausnitzii, a microorganism with positive effects in humans. Piglets might thus derive a competitive advantage from later weaning because they have more time to accumulate a higher diversity of potentially beneficial microbes prior to the stressful and risky weaning period.
Published: 2019

46. A High-Content Microscopy Screening Identifies New Genes Involved in Cell Width Control in Bacillus subtilis

Author: Arnaud Chastanet, Cyrille Billaudeau, Parfait Evouna-Mengue, Rut Carballido-López, Nathalie Deboosere, Dimitri Juillot, Charlène Cornilleau, Priscille Brodin, Véronique Léjard, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé [MICALIS], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], and MetaGenoPolis [MGP (US 1367)]
Subjects: cell division, carbon metabolism, Cell division, Physiology, Morphogenesis, cell width, Bacillus subtilis, Biochemistry, Microbiology, cell shape, Bacterial cell structure, chemistry.chemical_compound, Min System, Genetics, cell growth, Rod complex, Molecular Biology, HCS microscopy, Ecology, Evolution, Behavior and Systematics, biology, Cell growth, Cell cycle, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, Min system, Computer Science Applications, Cell biology, chemistry, Modeling and Simulation, cell wall, Peptidoglycan, metabolism, Research Article
Abstract: How cells control their shape and size is a fundamental question of biology. In most bacteria, cell shape is imposed by the peptidoglycan (PG) polymeric meshwork that surrounds the cell. Thus, bacterial cell morphogenesis results from the coordinated action of the proteins assembling and degrading the PG shell. Remarkably, during steady-state growth, most bacteria maintain a defined shape along generations, suggesting that error-proof mechanisms tightly control the process. In the rod-shaped model for the Gram-positive bacterium Bacillus subtilis, the average cell length varies as a function of the growth rate, but the cell diameter remains constant throughout the cell cycle and across growth conditions. Here, in an attempt to shed light on the cellular circuits controlling bacterial cell width, we developed a screen to identify genetic determinants of cell width in B. subtilis. Using high-content screening (HCS) fluorescence microscopy and semiautomated measurement of single-cell dimensions, we screened a library of ∼4,000 single knockout mutants. We identified 13 mutations significantly altering cell diameter, in genes that belong to several functional groups. In particular, our results indicate that metabolism plays a major role in cell width control in B. subtilis. IMPORTANCE Bacterial shape is primarily dictated by the external cell wall, a vital structure that, as such, is the target of countless antibiotics. Our understanding of how bacteria synthesize and maintain this structure is therefore a cardinal question for both basic and applied research. Bacteria usually multiply from generation to generation while maintaining their progenies with rigorously identical shapes. This implies that the bacterial cells constantly monitor and maintain a set of parameters to ensure this perpetuation. Here, our study uses a large-scale microscopy approach to identify at the whole-genome level, in a model bacterium, the genes involved in the control of one of the most tightly controlled cellular parameters, the cell width.
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47. The new science of metagenomics and the challenges of its use in both developed and developing countries

Author: Prifti, Edi, Zucker, Jean-Daniel, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MSI, Institut de la francophonie pour l'informatique (IFI), Agence universitaire de la francophonie-Agence universitaire de la francophonie, Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Institut de Recherche pour le Développement (IRD)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA), MetaQuant, Institut National de la Recherche Agronomique (INRA), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Université Pierre et Marie Curie - Paris 6 (UPMC), Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Cadi Ayyad [Marrakech] (UCA)-Universtié Yaoundé 1 [Cameroun]-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Université Pierre et Marie Curie - Paris 6 (UPMC), Département Microbiologie et Chaîne Alimentaire ( MICA ), Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Recherche Agronomique ( INRA ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de la francophonie pour l'informatique ( IFI ), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] ( UMMISCO ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop ( UCAD ) -Université Gaston Bergé (Saint-Louis, Sénégal)-Universtié Yaoundé 1 [Cameroun]-University Cadi Ayyad ( UCA )
Subjects: [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Quantitative Biology - Quantitative Methods, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, FOS: Biological sciences, ACM : H.: Information Systems/H.2: DATABASE MANAGEMENT/H.2.8: Database Applications/H.2.8.0: Data mining, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Metagenomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Quantitative Methods (q-bio.QM), ACM: H.: Information Systems/H.2: DATABASE MANAGEMENT/H.2.8: Database Applications/H.2.8.0: Data mining
Abstract: Our view of the microbial world and its impact on human health is changing radically with the ability to sequence uncultured or unculturable microbes sampled directly from their habitats, ability made possible by fast and cheap next generation sequencing technologies. Such recent developments represents a paradigmatic shift in the analysis of habitat biodiversity, be it the human, soil or ocean microbiome. We review here some research examples and results that indicate the importance of the microbiome in our lives and then discus some of the challenges faced by metagenomic experiments and the subsequent analysis of the generated data. We then analyze the economic and social impact on genomic-medicine and research in both developing and developed countries. We support the idea that there are significant benefits in building capacities for developing high-level scientific research in metagenomics in developing countries. Indeed, the notion that developing countries should wait for developed countries to make advances in science and technology that they later import at great cost has recently been challenged.
Published: 2013

48. Gut Microbiota Resilience: Definition, Link to Health and Strategies for Intervention

Author: Shaillay Kumar Dogra, Joël Doré, Sami Damak, Nestlé Centre R & D [Lausanne, Suisse], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nestle SA, and European Project: 788191,Homo.symbiosus
Subjects: Microbiology (medical), media_common.quotation_subject, Mini Review, [SDV]Life Sciences [q-bio], lcsh:QR1-502, microbiome, Disease, Biology, Gut flora, Microbiology, digestive system, lcsh:Microbiology, 03 medical and health sciences, fluids and secretions, Intervention (counseling), Environmental health, medicine, Microbiome, resilience, 030304 developmental biology, media_common, 0303 health sciences, 030306 microbiology, High fat diet, health, biology.organism_classification, medicine.disease, 3. Good health, stomatognathic diseases, Psychological resilience, Dysbiosis, probiotic, fiber
Abstract: International audience; The gut microbiota is a new frontier in health and disease. Not only many diseases are associated with perturbed microbiota, but an increasing number of studies point to a cause-effect relationship. Defining a healthy microbiota is not possible at the current state of our knowledge mostly because of high interindividual variability. A resilient microbiota could be used as surrogate for healthy microbiota. In addition, the gut microbiota is an "organ" with frontline exposure to environmental changes and insults. During the lifetime of an individual, it is exposed to challenges such as unhealthy diet, medications and infections. Impaired ability to bounce back to the pre-challenge baseline may lead to dysbiosis. It is therefore legitimate to postulate that maintaining a resilient microbiota may be important for health. Here we review the concept of resilience, what is known about the characteristics of a resilient microbiota, and how to assess microbiota resilience experimentally using a model of high fat diet challenge in humans. Interventions to maintain microbiota resilience can be guided by the knowledge of what microbial species or functions are perturbed by challenges, and designed to replace diminished species with probiotics, when available, or boost them with prebiotics. Fibers with multiple structures and composition can also be used to increase microbiota diversity, a characteristic of the microbiota that may be associated with resilience. We finally discuss some open questions and knowledge gaps.
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