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2. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

Author

Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf

Published
2023
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3. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Published
2022
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4. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author

Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Schmidt, Thomas S. B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean-Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc-Emmanuel, Ehrlich, S. Dusko, and Pedersen, Oluf

Published
2022
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7. Combinatorial, additive and dose-dependent drug–microbiome associations

Author

Forslund, Sofia K., Chakaroun, Rima, Zimmermann-Kogadeeva, Maria, Markó, Lajos, Aron-Wisnewsky, Judith, Nielsen, Trine, Moitinho-Silva, Lucas, Schmidt, Thomas S. B., Falony, Gwen, Vieira-Silva, Sara, Adriouch, Solia, Alves, Renato J., Assmann, Karen, Bastard, Jean-Philippe, Birkner, Till, Caesar, Robert, Chilloux, Julien, Coelho, Luis Pedro, Fezeu, Leopold, Galleron, Nathalie, Helft, Gerard, Isnard, Richard, Ji, Boyang, Kuhn, Michael, Le Chatelier, Emmanuelle, Myridakis, Antonis, Olsson, Lisa, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Tremaroli, Valentina, Valles-Colomer, Mireia, Lewinter, Christian, Søndertoft, Nadja B., Pedersen, Helle Krogh, Hansen, Tue H., Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Hercberg, Serge, Oppert, Jean-Michel, Letunic, Ivica, Nielsen, Jens, Bäckhed, Fredrik, Ehrlich, S. Dusko, Dumas, Marc-Emmanuel, Raes, Jeroen, Pedersen, Oluf, Clément, Karine, Stumvoll, Michael, and Bork, Peer

Published
2021
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8. Integration of time-series meta-omics data reveals how microbial ecosystems respond to disturbance

Author

Herold, Malte, Martínez Arbas, Susana, Narayanasamy, Shaman, Sheik, Abdul R., Kleine-Borgmann, Luise A. K., Lebrun, Laura A., Kunath, Benoît J., Roume, Hugo, Bessarab, Irina, Williams, Rohan B. H., Gillece, John D., Schupp, James M., Keim, Paul S., Jäger, Christian, Hoopmann, Michael R., Moritz, Robert L., Ye, Yuzhen, Li, Sujun, Tang, Haixu, Heintz-Buschart, Anna, May, Patrick, Muller, Emilie E. L., Laczny, Cedric C., and Wilmes, Paul

Published
2020
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11. Correction to: Microbiome definition re-visited: old concepts and new challenges

Author

Berg, Gabriele, Rybakova, Daria, Fischer, Doreen, Cernava, Tomislav, Vergès, Marie-Christine Champomier, Charles, Trevor, Chen, Xiaoyulong, Cocolin, Luca, Eversole, Kellye, Corral, Gema Herrero, Kazou, Maria, Kinkel, Linda, Lange, Lene, Lima, Nelson, Loy, Alexander, Macklin, James A., Maguin, Emmanuelle, Mauchline, Tim, McClure, Ryan, Mitter, Birgit, Ryan, Matthew, Sarand, Inga, Smidt, Hauke, Schelkle, Bettina, Roume, Hugo, Kiran, G. Seghal, Selvin, Joseph, de Souza, Rafael Soares Correa, van Overbeek, Leo, Singh, Brajesh K., Wagner, Michael, Walsh, Aaron, Sessitsch, Angela, and Schloter, Michael

Published
2020
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12. Microbiome definition re-visited: old concepts and new challenges

Author

Berg, Gabriele, Rybakova, Daria, Fischer, Doreen, Cernava, Tomislav, Vergès, Marie-Christine Champomier, Charles, Trevor, Chen, Xiaoyulong, Cocolin, Luca, Eversole, Kellye, Corral, Gema Herrero, Kazou, Maria, Kinkel, Linda, Lange, Lene, Lima, Nelson, Loy, Alexander, Macklin, James A., Maguin, Emmanuelle, Mauchline, Tim, McClure, Ryan, Mitter, Birgit, Ryan, Matthew, Sarand, Inga, Smidt, Hauke, Schelkle, Bettina, Roume, Hugo, Kiran, G. Seghal, Selvin, Joseph, Souza, Rafael Soares Correa de, van Overbeek, Leo, Singh, Brajesh K., Wagner, Michael, Walsh, Aaron, Sessitsch, Angela, and Schloter, Michael

Published
2020
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18. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in advanced non-small cell lung cancer patients

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Chatelier, Emmanuelle Le, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Subjects
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Humans, Immunologic Factors, Akkermansia, Immunotherapy, Article
Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) are needed. We previously reported in 100 NSCLC and kidney cancer patients that fecal Akkermansia muciniphila (Akk) correlated with ICI clinical success. The endpoint of this study was to prospectively validate the prognostic significance of fecal Akk in advanced NSCLC patients treated with first or second line ICI. We performed shotgun metagenomics-based microbiome profiling using two different pipelines in 338 NSCLC patients. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that could be useful for future studies as a tool to aid patient stratification.

Published
2022

20. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity:effect of biotin and prebiotic supplementation on improved metabolism

Author

Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, Clement, Karine, Commission of the European Communities, Medical Research Council (MRC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU 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), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Inst Med, Dept Mol & Clin Med, Wallenberg Lab, University of Gothenburg (GU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (COMUE) (USPC), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (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), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [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), Université de Bordeaux (UB), 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), Service de Diabétologie [CHU Pitié-Salpétrière], Laboratoire de chimie Macromoléculaire (CNRS UMR 5076), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Keck School of Medicine [Los Angeles], University of Southern California (USC), Nutrition et cerveau (U1213, U855), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Medicina Molecular, 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 - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK

Subjects
EXPRESSION, [SDV]Life Sciences [q-bio], Biotin, Endocrinology and Diabetes, Microbiology, DIET, Mice, Humans, Animals, Obesity, CHROMIUM PICOLINATE, Inflammation, Science & Technology, OVERWEIGHT, Gastroenterology & Hepatology, Gastroenterology, 1103 Clinical Sciences, Gastrointestinal Microbiome, Obesity, Morbid, MetaCardis Consortium, Mice, Inbred C57BL, nutrition, Prebiotics, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, micronutrients, Other Clinical Medicine, diabetes mellitus, Vitamin B Complex, 1114 Paediatrics and Reproductive Medicine, intestinal bacteria, HEALTH, Life Sciences & Biomedicine
Abstract

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Published
2022

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

Author

Ranaivo, Harimalala, primary, Thirion, Florence, additional, Béra-Maillet, Christel, additional, Guilly, Susie, additional, Simon, Chantal, additional, Sothier, Monique, additional, Van Den Berghe, Laurie, additional, Feugier-Favier, Nathalie, additional, Lambert-Porcheron, Stéphanie, additional, Dussous, Isabelle, additional, Roger, Loïc, additional, Roume, Hugo, additional, Galleron, Nathalie, additional, Pons, Nicolas, additional, Le Chatelier, Emmanuelle, additional, Ehrlich, Stanislav Dusko, additional, Laville, Martine, additional, Doré, Joël, additional, and Nazare, Julie-Anne, additional

Published
2022
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22. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Author

Bel Lassen, Pierre, Nielsen, Trine, Bergh, Per-Olof, Rouault, Christine, André, Sébastien, Marquet, Florian, Andreelli, Fabrizio, Salem, Joe-Elie, Assmann, Karen, Bastard, Jean-Philippe, Forslund, Sofia, Le Chatelier, Emmanuelle, Falony, Gwen, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Vieira-Silva, Sara, Hansen, Tue, Pedersen, Helle Krogh, Lewinter, Christian, Sønderskov, Nadja, Vestergaard, Henrik, Raes, Jeroen, Nielsen, Jens, Bork, Peer, Ehrlich, S. Dusko, Pedersen, Oluf, Aron-Wisneswky, Judith, Clément, Karine, Bäckhed, Fredrik, Molinaro, Antonio, Lassen, Pierre, Henricsson, Marcus, Wu, Hao, Adriouch, Solia, Belda, Eugeni, Chakaroun, Rima, Nielse, Trine, Bergh, Christine, Rouault, Sébastien, Andr, Florian, Marquet, Fabrizio, Andreelli, Joe-Elie, Salem, Karen, Assmann, Jean-Philippe, Bastard, Sofia, Forslund, Emmanuelle, Le Chatelier, Gwen, Falon, Nicolas, Pons, Edi, Prift, Benoit, Quinquis, Hugo, Roume, Sara, Vieira-Silv, Tue, Hansen, Krogh, Pedersen, Christian, Lewinter, Nadja, The, Metacardis, Køber, Lars, Vestergaar, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Galan, Pilar, Dumas, Marc-Emmanuel, Rae, Jeroen, Oppert, Jean-Michel, Letunic, Ivica, Nielse, Jens, Ehrlic, S, Stumvoll, Michael, Pederse, Oluf, Aron-Wisnewsky, Judith, Bäckhe, Fredrik, Sahlgrenska Center for Cardiovascular and Metabolic Research, Partenaires INRAE, Sahlgrenska University Hospital, 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 d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, 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), Medical Department III – Endocrinology, Nephrology, Rheumatology, Universität Leipzig [Leipzig], 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), Centre d'Investigation Clinique de Paris Est, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Tenon [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Experimental and Clinical Research Center [Berlin, Germany], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, 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), Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, Université Catholique de Louvain (UCL), VIB-KU Leuven Center for Microbiology [Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Sorbonne Université (SU)-Universtié Yaoundé 1 [Cameroun]-Université Cadi Ayyad [Marrakech] (UCA)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Institut de Recherche pour le Développement (IRD [France-Nord]), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), 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)-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), Department of Metabolism, Digestion and Reproduction, Imperial College London, National Heart and Lung Institute [London] (NHLI), Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), Biobyte Solutions GMBH, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Sahlgrenska Academy at University of Gothenburg [Göteborg], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rega Institute for Medical Research [Leuven, België], 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], 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]), Chalmers University of Technology [Göteborg], European Molecular Biology Laboratory [Heidelberg] (EMBL), 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), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, HAL-SU, Gestionnaire, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord-Institut National Agronomique Paris-Grignon (INA P-G)-Sorbonne Université (SU)-CETAF-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Auteur indépendant, Commission of the European Communities, and Universität Leipzig

Subjects
0301 basic medicine, Male, ACCURATE METHOD, endocrine system diseases, Metabolite, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Type 2 diabetes, GUT MICROBIOME, GLUCOSE, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, [CHIM] Chemical Sciences, Prediabetes, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, biology, INSULIN SENSITIVITY, Imidazoles, HOMEOSTASIS MODEL ASSESSMENT, Middle Aged, 3. Good health, Multidisciplinary Sciences, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Enterotype, Female, Adult, medicine.medical_specialty, Science, Carbohydrate metabolism, Microbiology, digestive system, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, INTESTINAL MICROBIOTA, Internal medicine, medicine, Humans, [CHIM]Chemical Sciences, Histidine, Author Correction, PHYSIOLOGY, Aged, Science & Technology, Bacteria, General Chemistry, Metabolism, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, MetaCardis Consortium, METAGENOME, INDIVIDUALS, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, lcsh:Q, Bacteroides
Abstract

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism., Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Published
2020

23. Long inverted repeats around the chromosome replication terminus in the model strain Bacillus thuringiensis serovar israelensis BGSC 4Q7

Author

Bolotin, Alexander, Quinquis, Benoit, Roume, Hugo, Gohar, Michel, Lereclus, Didier, and Sorokin, Alexei

Subjects
DNA Replication, BGSC strains, Whole Genome Sequencing, Prophages, replication termination, Inverted Repeat Sequences, Bacillus thuringiensis, High-Throughput Nucleotide Sequencing, Chromosomes, Bacterial, Serogroup, plasmid-chromosome association, chromosome structure, Microbial evolution and epidemiology: Mechanisms of evolution, Selection, Genetic, long inverted repeats, Research Article, Plasmids
Abstract

Bacillus thuringiensis serovar israelensis is the most widely used natural biopesticide against mosquito larvae worldwide. Its lineage has been actively studied and a plasmid-free strain, B . thuringiensis serovar israelensis BGSC 4Q7 (4Q7), has been produced. Previous sequencing of the genome of this strain has revealed the persistent presence of a 235 kb extrachromosomal element, pBtic235, which has been shown to be an inducible prophage, although three putative chromosomal prophages have been lost. Moreover, a 492 kb region, potentially including the standard replication terminus, has also been deleted in the 4Q7 strain, indicating an absence of essential genes in this area. We reanalysed the genome coverage distribution of reads for the previously sequenced variant strain, and sequenced two independently maintained samples of the 4Q7 strain. A 553 kb area, close to the 492 kb deletion, was found to be duplicated. This duplication presumably restored the equal sizes of the replichores, and a balanced functioning of replication termination. An analysis of genome assembly graphs revealed a transient association of the host chromosome with the pBtic235 element. This association may play a functional role in the replication of the bacterial chromosome, and the termination of this process in particular. The genome-restructuring events detected may modify the genetic status of cytotoxic or haemolytic toxins, potentially influencing strain virulence. Twelve of the single-nucleotide variants identified in 4Q7 were probably due to the procedure used for strain construction or were present in the precursor of this strain. No sequence variants were found in pBtic235, but the distribution of the corresponding 4Q7 reads indicates a significant difference from counterparts in natural B. thuringiensis serovar israelensis strains, suggesting a duplication or over-replication in 4Q7. Thus, the 4Q7 strain is not a pure plasmid-less offshoot, but a highly genetically modified derivative of its natural ancestor. In addition to potentially influencing virulence, genome-restructuring events can modify the replication termination machinery. These findings have potential implications for the conclusions of virulence studies on 4Q7 as a model, but they also raise interesting fundamental questions about the functioning of the Bacillus genome.

Published
2020

24. Additional file 1 of Microbiome definition re-visited: old concepts and new challenges

Author

Berg, Gabriele, Rybakova, Daria, Fischer, Doreen, Cernava, Tomislav, Marie-Christine Champomier Vergès, Charles, Trevor, Xiaoyulong Chen, Cocolin, Luca, Kellye Eversole, Corral, Gema Herrero, Kazou, Maria, Kinkel, Linda, Lange, Lene, Lima, Nelson, Loy, Alexander, Macklin, James A., Maguin, Emmanuelle, Mauchline, Tim, McClure, Ryan, Mitter, Birgit, Ryan, Matthew, Sarand, Inga, Smidt, Hauke, Schelkle, Bettina, Roume, Hugo, G. Seghal Kiran, Selvin, Joseph, Souza, Rafael Soares Correa De, Overbeek, Leo Van, Brajesh K. Singh, Wagner, Michael, Walsh, Aaron, Sessitsch, Angela, and Schloter, Michael

Subjects
Data_FILES
Abstract

Additional file 1.

Published
2020
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26. Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients

Author

Derosa, Lisa, primary, Routy, Bertrand, additional, Fidelle, Marine, additional, Iebba, Valerio, additional, Alla, Laurie, additional, Pasolli, Edoardo, additional, Segata, Nicola, additional, Desnoyer, Aude, additional, Pietrantonio, Filippo, additional, Ferrere, Gladys, additional, Fahrner, Jean-Eudes, additional, Le Chatellier, Emmanuelle, additional, Pons, Nicolas, additional, Galleron, Nathalie, additional, Roume, Hugo, additional, Duong, Connie P.M., additional, Mondragón, Laura, additional, Iribarren, Kristina, additional, Bonvalet, Mélodie, additional, Terrisse, Safae, additional, Rauber, Conrad, additional, Goubet, Anne-Gaëlle, additional, Daillère, Romain, additional, Lemaitre, Fabien, additional, Reni, Anna, additional, Casu, Beatrice, additional, Alou, Maryam Tidjani, additional, Alves Costa Silva, Carolina, additional, Raoult, Didier, additional, Fizazi, Karim, additional, Escudier, Bernard, additional, Kroemer, Guido, additional, Albiges, Laurence, additional, and Zitvogel, Laurence, additional

Published
2020
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27. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

Author

Meslier, Victoria, primary, Laiola, Manolo, additional, Roager, Henrik Munch, additional, De Filippis, Francesca, additional, Roume, Hugo, additional, Quinquis, Benoit, additional, Giacco, Rosalba, additional, Mennella, Ilario, additional, Ferracane, Rosalia, additional, Pons, Nicolas, additional, Pasolli, Edoardo, additional, Rivellese, Angela, additional, Dragsted, Lars Ove, additional, Vitaglione, Paola, additional, Ehrlich, Stanislav Dusko, additional, and Ercolini, Danilo, additional

Published
2020
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28. Two-month consumption of bread enriched with a fiber mix: impact on gut microbiota and cardiometabolic profile in at cardiometabolic-risk subjects.

Author

Ranaivo, Harimalala, primary, Guilly, Susie, additional, Sothier, Monique, additional, Van Den Berghe, Laurie, additional, Lambert-Porcheron, Stéphanie, additional, Dussous, Isabelle, additional, Roger, Loïc, additional, Béra-Maillet, Christel, additional, Roume, Hugo, additional, Galleron, Nathalie, additional, Pons, Nicolas, additional, Le Chatelier, Emmanuelle, additional, Ehrlich, Dusko, additional, Laville, Martine, additional, Doré, Joël, additional, and Nazare, Julie-Anne, additional

Published
2020
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29. 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

Cox, Selina R., primary, Lindsay, James O., additional, Fromentin, Sébastien, additional, Stagg, Andrew J., additional, McCarthy, Neil E., additional, Galleron, Nathalie, additional, Ibraim, Samar B., additional, Roume, Hugo, additional, Levenez, Florence, additional, Pons, Nicolas, additional, Maziers, Nicolas, additional, Lomer, Miranda C., additional, Ehrlich, S. Dusko, additional, Irving, Peter M., additional, and Whelan, Kevin, additional

Published
2020
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30. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Author

Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E, Prifti, Edi, Aron-Wisnewsky, Judith, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloé, André, Sébastien, Andreelli, Fabrizio, Blu¨her, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H, Holmes, Bridget, Ji, Boyang, Krogh Pedersen, Helle, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Mannerås-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B, Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Ba¨ckhed, Fredrik, Raes, Jeroen, and Clément, Karine

Abstract

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Published
2022
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31. Intestinal Akkermansia muciniphilapredicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

Author

Derosa, Lisa, Routy, Bertrand, Thomas, Andrew Maltez, Iebba, Valerio, Zalcman, Gerard, Friard, Sylvie, Mazieres, Julien, Audigier-Valette, Clarisse, Moro-Sibilot, Denis, Goldwasser, François, Silva, Carolina Alves Costa, Terrisse, Safae, Bonvalet, Melodie, Scherpereel, Arnaud, Pegliasco, Hervé, Richard, Corentin, Ghiringhelli, François, Elkrief, Arielle, Desilets, Antoine, Blanc-Durand, Felix, Cumbo, Fabio, Blanco, Aitor, Boidot, Romain, Chevrier, Sandy, Daillère, Romain, Kroemer, Guido, Alla, Laurie, Pons, Nicolas, Le Chatelier, Emmanuelle, Galleron, Nathalie, Roume, Hugo, Dubuisson, Agathe, Bouchard, Nicole, Messaoudene, Meriem, Drubay, Damien, Deutsch, Eric, Barlesi, Fabrice, Planchard, David, Segata, Nicola, Martinez, Stéphanie, Zitvogel, Laurence, Soria, Jean-Charles, and Besse, Benjamin

Abstract

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila(Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n= 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium halliiand Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.

Published
2022
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32. Identification of rumen microbial biomarkers linked to methane emission in Holstein dairy cows

Author

Ramayo‐Caldas, Yuliaxis, primary, Zingaretti, Laura, additional, Popova, Milka, additional, Estellé, Jordi, additional, Bernard, Aurelien, additional, Pons, Nicolas, additional, Bellot, Pau, additional, Mach, Núria, additional, Rau, Andrea, additional, Roume, Hugo, additional, Perez‐Enciso, Miguel, additional, Faverdin, Philippe, additional, Edouard, Nadège, additional, Ehrlich, Dusko, additional, Morgavi, Diego P., additional, and Renand, Gilles, additional

Published
2019
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33. Identification of rumen microbial biomarkers linked to methane emission in Holstein dairy cows.

Author

Ramayo‐Caldas, Yuliaxis, Zingaretti, Laura, Popova, Milka, Estellé, Jordi, Bernard, Aurelien, Pons, Nicolas, Bellot, Pau, Mach, Núria, Rau, Andrea, Roume, Hugo, Perez‐Enciso, Miguel, Faverdin, Philippe, Edouard, Nadège, Ehrlich, Dusko, Morgavi, Diego P., and Renand, Gilles

Subjects
GREENHOUSE gas mitigation, CATTLE industry, COWS, BIOMARKERS, DAIRY industry, REDUCTASES, RIBOSOMAL RNA, DISCRIMINANT analysis
Abstract

Mitigation of greenhouse gas emissions is relevant for reducing the environmental impact of ruminant production. In this study, the rumen microbiome from Holstein cows was characterized through a combination of 16S rRNA gene and shotgun metagenomic sequencing. Methane production (CH4) and dry matter intake (DMI) were individually measured over 4–6 weeks to calculate the CH4 yield (CH4y = CH4/DMI) per cow. We implemented a combination of clustering, multivariate and mixed model analyses to identify a set of operational taxonomic unit (OTU) jointly associated with CH4y and the structure of ruminal microbial communities. Three ruminotype clusters (R1, R2 and R3) were identified, and R2 was associated with higher CH4y. The taxonomic composition on R2 had lower abundance of Succinivibrionaceae and Methanosphaera, and higher abundance of Ruminococcaceae, Christensenellaceae and Lachnospiraceae. Metagenomic data confirmed the lower abundance of Succinivibrionaceae and Methanosphaera in R2 and identified genera (Fibrobacter and unclassified Bacteroidales) not highlighted by metataxonomic analysis. In addition, the functional metagenomic analysis revealed that samples classified in cluster R2 were overrepresented by genes coding for KEGG modules associated with methanogenesis, including a significant relative abundance of the methyl‐coenzyme M reductase enzyme. Based on the cluster assignment, we applied a sparse partial least‐squares discriminant analysis at the taxonomic and functional levels. In addition, we implemented a sPLS regression model using the phenotypic variation of CH4y. By combining these two approaches, we identified 86 discriminant bacterial OTUs, notably including families linked to CH4 emission such as Succinivibrionaceae, Ruminococcaceae, Christensenellaceae, Lachnospiraceae and Rikenellaceae. These selected OTUs explained 24% of the CH4y phenotypic variance, whereas the host genome contribution was ~14%. In summary, we identified rumen microbial biomarkers associated with the methane production of dairy cows; these biomarkers could be used for targeted methane‐reduction selection programmes in the dairy cattle industry provided they are heritable. [ABSTRACT FROM AUTHOR]

Published
2020
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36. Comparative integrated omics: identification of key functionalities in microbial community-wide metabolic networks

Author

Jarosz, Yohan, Herold, Malte, Kaysen, Anne, Pinel, Nicolas, Roume, Hugo, Heintz-Buschart, Anna, Muller, Emilie, May, Patrick, Satagopam, Venkata, Laczny, Cédric, Narayanasamy, Shaman, Lebrun, Laura, Hoopmann, Michael, Schupp, James, Gillece, John, Hicks, Nathan, Engelthaler, David, Sauter, Thomas, Keim, Paul, Moritz, Robert, Wilmes, Paul, ALYOTECH TS&I, ALYOTECH, Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg [Luxembourg], European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany, Université du Luxembourg (Uni.lu), Center for Microbial Genetics and Genomics, Northern Arizona University [Flagstaff], Section des Sciences de la Terre, and University of Geneva [Switzerland]

Subjects
[SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, 030306 microbiology, Community structure, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Computational biology, 15. Life on land, Biology, Applied Microbiology and Biotechnology, Microbiology, Article, 6. Clean water, Transcriptome, 03 medical and health sciences, Metagenomics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Metaproteomics, Identification (biology), [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Keystone species, Gene, Function (biology), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Biotechnology
Abstract

Mixed microbial communities underpin important biotechnological processes such as biological wastewater treatment (BWWT). A detailed knowledge of community structure and function relationships is essential for ultimately driving these systems towards desired outcomes, e.g., the enrichment in organisms capable of accumulating valuable resources during BWWT. A comparative integrated omic analysis including metagenomics, metatranscriptomics and metaproteomics was carried out to elucidate functional differences between seasonally distinct oleaginous mixed microbial communities (OMMCs) sampled from an anoxic BWWT tank. A computational framework for the reconstruction of community-wide metabolic networks from multi-omic data was developed. These provide an overview of the functional capabilities by incorporating gene copy, transcript and protein abundances. To identify functional genes, which have a disproportionately important role in community function, we define a high relative gene expression and a high betweenness centrality relative to node degree as gene-centric and network topological features, respectively. Genes exhibiting high expression relative to gene copy abundance include genes involved in glycerolipid metabolism, particularly triacylglycerol lipase, encoded by known lipid accumulating populations, e.g., Candidatus Microthrix parvicella. Genes with a high relative gene expression and topologically important positions in the network include genes involved in nitrogen metabolism and fatty acid biosynthesis, encoded by Nitrosomonas spp. and Rhodococcus spp. Such genes may be regarded as ‘keystone genes’ as they are likely to be encoded by keystone species. The linking of key functionalities to community members through integrated omics opens up exciting possibilities for devising prediction and control strategies for microbial communities in the future. Charting metabolic activity in diverse microbial communities could help scientists control the behavior of these communities, new research shows. Paul Wilmes and colleagues at the University of Luxembourg, alongside scientists from the United States, set out to characterize the biological function of bacterial communities—normally a daunting task due to the sheer number of species involved. To accomplish this, Wilmes and colleagues took a community-wide approach, collecting genomic, transcriptomic and proteomic data from lipid-accumulating microbial consortia in a wastewater treatment tank and assembling functional maps reflecting overall biochemical processes. The scientists were then able to identify ‘keystone’ genes that play a critical role in the community—for example, genes involved in fatty acid biosynthesis were particularly prominent. Such findings could guide strategies for manipulating microbial communities for optimized disease control or biofuel production in future.

Published
2015

41. Comparative integrated omics: identification of key functionalities in microbial community-wide metabolic networks

Author

Roume, Hugo, Buschart, Anna, Muller, Emilie, May, Patrick, Satagopam, Venkata, Laczny, Cedric Christian, Narayanasamy, Shaman, Lebrun, Laura, Hoopmann, Michael, Schupp, James, Gillece, John, Hicks, Nathan, Engelthaler, David, Sauter, Thomas, Keim, Paul, Moritz, Robert, Wilmes, Paul, Fonds National de la Recherche - FnR [sponsor], National Science Foundation [sponsor], National Institute of General Medical Sciences [sponsor], Luxembourg Centre for Systems Biomedicine (LCSB): Eco-Systems Biology (Wilmes Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Institute for Systems Biology (ISB) [research center], The Translational Genomic Research Institute-North (Tgen) [research center], University of Luxembourg: High Performance Computing - ULHPC [research center], and University of Luxembourg: Life Science Research Unit [research center]

Subjects
Environmental sciences & ecology [F08] [Life sciences], Sciences de l'environnement & écologie [F08] [Sciences du vivant], Microbiologie [F11] [Sciences du vivant], Microbiology [F11] [Life sciences], Genetics & genetic processes [F10] [Life sciences], Génétique & processus génétiques [F10] [Sciences du vivant]
Abstract

BACKGROUND: Mixed microbial communities underpin important biotechnological processes such as biological wastewater treatment (BWWT). A detailed knowledge of community structure and function relationships is essential for ultimately driving these systems towards desired outcomes, e.g., the enrichment in organisms capable of accumulating valuable resources during BWWT. METHODS: A comparative integrated omic analysis including metagenomics, metatranscriptomics and metaproteomics was carried out to elucidate functional differences between seasonally distinct oleaginous mixed microbial communities (OMMCs) sampled from an anoxic BWWT tank. A computational framework for the reconstruction of community-wide metabolic networks from multi-omic data was developed. These provide an overview of the functional capabilities by incorporating gene copy, transcript and protein abundances. To identify functional genes, which have a disproportionately important role in community function, we define a high relative gene expression and a high betweenness centrality relative to node degree as gene-centric and network topological features, respectively. RESULTS: Genes exhibiting high expression relative to gene copy abundance include genes involved in glycerolipid metabolism, particularly triacylglycerol lipase, encoded by known lipid accumulating populations, e.g., Candidatus Microthrix parvicella. Genes with a high relative gene expression and topologically important positions in the network include genes involved in nitrogen metabolism and fatty acid biosynthesis, encoded by Nitrosomonas spp. and Rhodococcus spp. Such genes may be regarded as ‘keystone genes’ as they are likely to be encoded by keystone species. CONCLUSION: The linking of key functionalities to community members through integrated omics opens up exciting possibilities for devising prediction and control strategies for microbial communities in the future.

Published
2015

43. MOESM1 of Electrolytic extraction drives volatile fatty acid chain elongation through lactic acid and replaces chemical pH control in thin stillage fermentation

Author

Andersen, Stephen, Candry, Pieter, Thais Basadre, Khor, Way, Roume, Hugo, Hernandez-Sanabria, Emma, Coma, Marta, and Korneel Rabaey

Subjects
food and beverages
Abstract

Additional file 1. Further information on composition and microbial community abundance in the applied current and control thin stillage fermentations.

Published
2015
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45. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author

Vieira-Silva, Sara, Falony, Gwen, Belda, Eugeni, Nielsen, Trine, Aron-Wisnewsky, Judith, Chakaroun, Rima, Forslund, Sofia K., Assmann, Karen, Valles-Colomer, Mireia, Nguyen, Thi Thuy Duyen, Proost, Sebastian, Prifti, Edi, Tremaroli, Valentina, Pons, Nicolas, Le Chatelier, Emmanuelle, Andreelli, Fabrizio, Bastard, Jean-Phillippe, Coelho, Luis Pedro, Galleron, Nathalie, Hansen, Tue H., Hulot, Jean-Sébastien, Lewinter, Christian, Pedersen, Helle K., Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Søndertoft, Nadja B., Touch, Sothea, Dumas, Marc-Emmanuel, Ehrlich, Stanislav Dusko, Galan, Pilar, Gøtze, Jens P., Hansen, Torben, Holst, Jens J., Køber, Lars, Letunic, Ivica, Nielsen, Jens, Oppert, Jean-Michel, Stumvoll, Michael, Vestergaard, Henrik, Zucker, Jean-Daniel, Bork, Peer, Pedersen, Oluf, Bäckhed, Fredrik, Clément, Karine, and Raes, Jeroen

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 Faecalibacteriumand 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 consistency3and inflammation status4during 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.

Published
2020
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49. Molecular Eco-Systems Biology of Lipid Accumulating Microbial Communities in Biological Wastewater Treatment Plants

Author

Roume, Hugo and Wilmes, Paul [superviser]

Subjects
Environmental sciences & ecology [F08] [Life sciences], Sciences de l'environnement & écologie [F08] [Sciences du vivant], Eco-Systems Biology, Triacyglycerol, Biofuel, Lipid Accumulating organism (LAO), Community-wide metabolic networks, Biochemistry, biophysics & molecular biology [F05] [Life sciences], Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], Wastewater Treatment Plant (WWTP), Long chain fatty acid, Microthrix parvicella
Abstract

Biological wastewater treatment is based on the use of microorganisms capable of intense metabolic activity that results in the removal of a large proportion of organic and inorganic contaminants. Given copious amounts of energy-dense organic molecules such as lipids accumulated by the microbial biomass, chemical energy may be directly harnessed from this for biofuel production. Here, lipid accumulating organism (LAO)-enriched microbial communities were studied using a molecular eco-systems biology approach. This involved the development of necessary methodologies including a new comprehensive biomolecular extraction method, yielding high-quality DNA, RNA, proteins and metabolites, as well as bioinformatic approaches for integrating and analysing the derived high-throughput genomic, transcriptomic, proteomic and metabolomic data. At the inception of the project, a full-scale wastewater treatment plant (WWTP) system with a strong presence of LAOs especially during winter months, i.e. the Schifflange WWTP (Esch-sur-Alzette, Luxembourg), was identified and selected for further study. 16S rRNA amplicon sequencing highlighted the presence of ubiquitous lipid accumulating bacteria closely related to Candidatus Microthrix parvicella which increase in abundance from autumn to winter over other highly abundant community members belonging to Alkanindiges spp. and Acinetobacter spp. In order to elucidate compositional, genetic and functional differences between autumn and winter LAO communities, a comparative integrative omic analysis was carried out on rationally selected autumn and winter LAO community samples. The results from metabolomic/lipidomic analyses between intra- and extracellular compartments support previous models of uptake of unprocessed long chain fatty acids (LCFAs) from the wastewater environment and their storage as triacyglycerols within LAOs. Furthermore, a tailored computational framework for the integration of multi-omic datasets into reconstructed community-wide metabolic networks and models was developed. The resulting networks provide overviews of functional capacity of the sampled LAO communities by incorporating gene copy numbers, transcript levels and protein frequency across the two studied environmental conditions. The identification of genes overexpressed, strongly associated with a specific season and/or possessing a high clustering coefficient suggests the existence of keystone genes, analogous to keystone species in species interaction networks. Examples of such keystone genes in the context of the LAO communities include genes coding for proteins involved in nitrogen and glycerolipid metabolism. The existence of such keystone genes opens up exciting possibilities for prediction and control strategies of microbial communities at the dawn of the field of Eco-Systems Biology.

Published
2013

50. Comparative integrated omics: identification of key functionalities in microbial community-wide metabolic networks

Author

Roume, Hugo, primary, Heintz-Buschart, Anna, additional, Muller, Emilie E L, additional, May, Patrick, additional, Satagopam, Venkata P, additional, Laczny, Cédric C, additional, Narayanasamy, Shaman, additional, Lebrun, Laura A, additional, Hoopmann, Michael R, additional, Schupp, James M, additional, Gillece, John D, additional, Hicks, Nathan D, additional, Engelthaler, David M, additional, Sauter, Thomas, additional, Keim, Paul S, additional, Moritz, Robert L, additional, and Wilmes, Paul, additional

Published
2015
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