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1. Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism

Author

Guillaume Dalmasso, Racha Beyrouthy, Sandrine Brugiroux, Etienne Ruppé, Laurent Guillouard, Virginie Bonnin, Pierre Saint-Sardos, Amine Ghozlane, Vincent Gaumet, Nicolas Barnich, Julien Delmas, Richard Bonnet, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), This study was supported by the Ministère de la Recherche et de la Technologie, the Inserm (UMR 1071), the INRAe (USC-2018), the French government’s IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25), the National Program ‘Microbiote’ Inserm, the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) programme TransComp-ESC-R of the European Commission, and a grant (‘DYASPEO’) from the national priority research program for antimicrobial resistance (PPR-AMR)., ANR-20-PAMR-0003,DYASPEO,Dynamics, AMR, spread, persistence, evolution, colonization, human, animal, environment(2020), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), and European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012)

Subjects
Microbiology (medical), Inflammation, Virulence, Colistin, Antibiotic resistance, Microbiota, [SDV]Life Sciences [q-bio], Escherichia coli, Antimicrobial peptides, mcr-1, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Microbiology, Commensalism
Abstract

Background The plasmid-mediated resistance gene mcr-1 confers colistin resistance in Escherichia coli and paves the way for the evolution to pan-drug resistance. We investigated the impact of mcr-1 in gut colonization in the absence of antibiotics using isogenic E. coli strains transformed with a plasmid encoding or devoid of mcr-1. Results In gnotobiotic and conventional mice, mcr-1 significantly enhanced intestinal anchoring of E. coli but impaired their lethal effect. This improvement of intestinal fitness was associated with a downregulation of intestinal inflammatory markers and the preservation of intestinal microbiota composition. The mcr-1 gene mediated a cross-resistance to antimicrobial peptides secreted by the microbiota and intestinal epithelial cells (IECs), enhanced E. coli adhesion to IECs, and decreased the proinflammatory activity of both E. coli and its lipopolysaccharides. Conclusion Overall, mcr-1 changed multiple facets of bacterial behaviour and appeared as a factor enhancing commensal lifestyle and persistence in the gut even in the absence of antibiotics.

Published
2023

2. Role of adherent and invasive Escherichia coli in Crohn’s disease: lessons from the postoperative recurrence model

Author

Anthony Buisson, Harry Sokol, Nassim Hammoudi, Stéphane nancey, Xavier Treton, Maria Nachury, Mathurin Fumery, Xavier Hébuterne, Michael Rodrigues, Jean-Pierre Hugot, Gilles Boschetti, Carmen Stefanescu, Pauline Wils, Philippe Seksik, Lionel Le Bourhis, Madeleine Bezault, Pierre Sauvanet, Bruno Pereira, Matthieu Allez, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), 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), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Servcie Hépato-gastroentérolgie et Nutrition clinique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Remind Study Group, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], Unité de Biostatistiques [CHU Clermont-Ferrand], MSD France, Association François Aupetit, Helmsley Charitable Trust, Ministère de la Recherche et de la Technologie, Inserm (UMR 1071), University of Clermont Auvergne, Inserm {National Programme 'Microbiote'], INRAE (USC-2018), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract

ObjectiveWe used the postoperative recurrence model to better understand the role of adherent and invasiveEscherichia coli(AIEC) bacteria in Crohn’s disease (CD), taking advantage of a well-characterised postoperative cohort.DesignFrom a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts’ index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders.ResultsAIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (pRuminococcus gnavus.ConclusionBased on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD.Trial registration numberNCT03458195.

Published
2022

3. Beneficial Effects of High Intensity Interval Training and/or Linseed Oil Supplementation to Limit Obesity-Induced Oxidative Stress in High Fat Diet-Fed Rats

Author

Laurie Josset, Claire Plissonneau, Carole Groussard, Vincent Pialoux, Nicolas Barnich, Mathilde Mura, Guillaume Mairesse, Nathalie Boisseau, Frédéric Capel, Guillaume Chesneau, Etienne Gouraud, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Valorex, This research was funded by grants from Valorex. The authors are also supported by the Ministère de la Recherche et de la Technologie (M2iSH and AME2P Unit), Inserm (UMR 1071), INRAE (USC-2018) and by the French government IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25), I-SITE project (CAP 2025) of the University of Clermont Auvergne., ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Jonchère, Laurent, and CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID

Subjects
Male, obesity, Antioxidant, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Adipose tissue, High-Intensity Interval Training, medicine.disease_cause, Interval training, Antioxidants, 0302 clinical medicine, Subcutaneous Tissue, Linseed oil, oxidative stress, TX341-641, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, biology, Chemistry, high fat diet, food and beverages, Catalase, Up-Regulation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Liver, High-intensity interval training, Subcutaneous tissue, medicine.medical_specialty, food.ingredient, Linseed Oil, high intensity interval training, Article, 03 medical and health sciences, food, Internal medicine, medicine, Animals, Rats, Wistar, 030304 developmental biology, Nitrates, Nutrition. Foods and food supply, Superoxide Dismutase, Feeding Behavior, linseed oil supplementation, Endocrinology, Dietary Supplements, biology.protein, 030217 neurology & neurosurgery, Oxidative stress, Biomarkers, Food Science
Abstract

International audience; High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.

Published
2021

4. When Pathobiont-Carbohydrate Interaction Turns Bittersweet!

Author

Nicolas Barnich, Benoit Chassaing, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Kenneth Rainin Foundation, National Program 'Microbiote' INSERM, Ministere de la Recherche et de la Technologie, INSERM (UMR 1071), INRAe (USC-2018, Universite Clermont Auvergne [I-SITE project (CAP 2025)], Association Francois Aupetit, ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), European Project: ERC-2018-StG804135, ROSSI, Sabine, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, and Mucus-Penetrating Microbiota: Characterization, Mechanism and Therapeutic in Metabolic Disease - ERC-2018-StG804135 - INCOMING

Subjects
Phosphotransferase System, NCBI, National Center for Biotechnology Information, PTS, phosphotransferase system, EIIA, enzyme IIA, Carbohydrates, Gene Expression, RC799-869, Computational biology, Biology, cDNA, complementary DNA, PCR, polymerase chain reaction, ComputingMilieux_MISCELLANEOUS, Original Research, Hepatology, IBD, inflammatory bowel disease, Gastroenterology, RNA-seq, RNA sequencing, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diseases of the digestive system. Gastroenterology, Carbohydrate, Inflammatory Bowel Diseases, WT, wild-type, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, mRNA, messenger RNA, IL, interleukin, rRNA, ribosomal RNA, Ct, cycle threshold, BHI, brain heart infusion
Abstract

Background & Aims The inflammatory bowel diseases (IBDs), Crohn’s disease and ulcerative colitis, are caused in part by aberrant immune responses to resident intestinal bacteria. Certain dietary components, including carbohydrates, are associated with IBDs and alter intestinal bacterial composition. However, the effects of luminal carbohydrates on the composition and colitogenic potential of intestinal bacteria are incompletely understood. We hypothesize that carbohydrate metabolism by resident proinflammatory intestinal bacteria enhances their growth and worsens intestinal inflammation. Methods We colonized germ-free, wild-type, and colitis-susceptible interleukin-10 knockout mice (Il10-/-) with a consortium of resident intestinal bacterial strains and quantified colon inflammation using blinded histologic scoring and spontaneous secretion of IL12/23p40 by colon explants. We measured luminal bacterial composition using real-time 16S polymerase chain reaction, bacterial gene expression using RNA sequencing and real-time polymerase chain reaction, and luminal glucosamine levels using gas chromatography–mass spectrometry. Results We show that a consortium of 8 bacterial strains induces severe colitis in Il10-/- mice and up-regulates genes associated with carbohydrate metabolism during colitis. Specifically, Enterococcus faecalis strain OG1RF is proinflammatory and strongly up-regulates OG1RF_11616-11610, an operon that encodes genes of a previously undescribed phosphotransferase system that we show imports glucosamine. Experimental colitis is associated with increased levels of luminal glucosamine and OG1RF_11616 causes worse colitis, not by increasing E faecalis numbers, but rather by mechanisms that require the presence of complex microbiota. Conclusions Further studies of luminal carbohydrate levels and bacterial carbohydrate metabolism during intestinal inflammation will improve our understanding of the pathogenesis of IBDs and may lead to the development of novel therapies for these diseases.

Published
2021

5. Successful dissemination of plasmid-mediated extended-Spectrum β-lactamases in enterobacterales over humans to wild fauna

Author

Richard Bonnet, Frédéric Robin, Patrícia Poeta, Racha Beyrouthy, Giberto Igrejas, Carolina Sabença, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Universidade de Trás-os-Montes e Alto Douro (UTAD), Universidade do Trás-os-Montes e Alto Douro, Laboratorio Associado para a Quimica Verde (LAQV), Requimte, Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto, Ministere de la Recherche et de la Technologie, Inserm (UMR 1071), INRAe (USC-2018), Programa de Accoes Universitarias Integradas Luso-Francesas [TC-14/2017], Portuguese Foundation for Science and Technology [[UID/QUI/50006/2019], ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), European Project: 323209,EC:FP7:HEALTH,FP7-JPROG-2012-RTD,JPIAMR(2012), Molé, Christine, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Coordination Action for the early implementation of the Joint Programming Initiative on Antimicrobial Resistance - JPIAMR - - EC:FP7:HEALTH2012-09-01 - 2016-02-29 - 323209 - VALID, Universidade do Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto-Departamento de Química (DQ), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)

Subjects
Microbiology (medical), QH301-705.5, medicine.disease_cause, Microbiology, Genome, Article, 03 medical and health sciences, Plasmid, Polymorphism (computer science), Virology, plasmid, medicine, Escherichia coli, IncI1-ST3, CTX-M-1, Biology (General), Gene, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Synteny, 2. Zero hunger, Genetics, 0303 health sciences, biology, 030306 microbiology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, β-lactamase, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multilocus sequence typing, beta-lactamase, Bacteria
Abstract

Background: The emergence of multidrug-resistant bacteria remains poorly understood in the wild ecosystem and at the interface of habitats. Here, we explored the spread of Escherichia coli containing IncI1-ST3 plasmid encoding resistance gene cefotaximase-Munich-1 (blaCTX-M-1) in human-influenced habitats and wild fauna using a genomic approach. Methods. Multilocus sequence typing (MLST), single-nucleotide polymorphism comparison, synteny-based analysis and data mining approaches were used to analyse a dataset of genomes and circularised plasmids. Results. CTX-M-1 E. coli sequence types (STs) were preferentially associated with ecosystems. Few STs were shared by distinct habitats. IncI1-ST3-blaCTX-M-1 plasmids are disseminated among all E. coli phylogroups. The main divergences in plasmids were located in a shuffling zone including blaCTX-M-1 inserted in a conserved site. This insertion hot spot exhibited diverse positions and orientations in a zone-modulating conjugation, and the resulting synteny was associated with geographic and biological sources. Conclusions. The ecological success of IncI1-ST3-blaCTX-M-1 appears less linked to the spread of their bacterial recipients than to their ability to transfer in a broad spectrum of bacterial lineages. This feature is associated with the diversity of their shuffling conjugation region that contain blaCTX-M-1. These might be involved in the resistance to antimicrobials, but also in their spread.

Published
2021

6. Beneficial Effects of Natural Mineral Waters on Intestinal Inflammation and the Mucosa-Associated Microbiota

Author

Michael Rodrigues, Sylvain Denis, Nicolas Barnich, Monique Alric, Danielle Faure-Imbert, C. Roques, Benoit Chassaing, Thierry Hanh, Caroline Chevarin, Olivier Le Goff, Pierre Sauvanet, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Suisse d'Electronique et de Microtechnique SA [Neuchatel] (CSEM), Centre Suisse d'Electronique et Microtechnique SA (CSEM), AllNext Consultants, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 'AFRETH' (Association francaise pour la recherche thermale) 2013-042021-02Ministere de la Recherche et de la Technologie INRAE (USC-2018) French government IDEX-ISITE initiative 16-IDEX-0001 (CAP 20-25)I-SITE project (CAP 2025) of the University of Clermont Auvergne European Research Council (ERC)ERC-2018-StG-804135Kenneth Rainin Foundation Inserm (UMR 1071), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Université de Toulouse (UT), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, Mice, chemistry.chemical_compound, 0302 clinical medicine, intestinal inflammation, mucosa-associated microbiota, Intestinal Mucosa, Biology (General), Spectroscopy, Mice, Inbred BALB C, Dextran Sulfate, General Medicine, Colitis, natural mineral water, 3. Good health, Computer Science Applications, Chemistry, Cytokine, Cytokines, 030211 gastroenterology & hepatology, medicine.symptom, QH301-705.5, Bicarbonate, Sodium, chemistry.chemical_element, Inflammation, Calcium, Article, Catalysis, Microbiology, Inorganic Chemistry, Lesion, 03 medical and health sciences, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Organic Chemistry, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, chemistry, Mineral Waters
Abstract

Natural mineral water (NMWs) intake has been traditionally used in the treatment of various gastrointestinal diseases. We investigated the effect of two French NMWs, one a calcium and magnesium sulphate, sodium chloride, carbonic, and ferruginous water (NMW1), the other a mainly bicarbonate water (NMW2) on the prevention of intestinal inflammation. Intestinal epithelial cells stimulated with heat inactivated Escherichia coli or H2O2 were treated with NMWs to evaluate the anti-inflammatory effects. Moderate colitis was induced by 1% dextran sulfate sodium (DSS) in Balbc/J mice drinking NMW1, NWW2, or control water. General signs and histological features of colitis, fecal lipocalin-2 and pro-inflammatory KC cytokine levels, global mucosa-associated microbiota, were analyzed. We demonstrated that both NMW1 and NMW2 exhibited anti-inflammatory effects using intestinal cells. In induced-colitis mice, NMW1 was effective in dampening intestinal inflammation, with significant reductions in disease activity scores, fecal lipocalin-2 levels, pro-inflammatory KC cytokine release, and intestinal epithelial lesion sizes. Moreover, NMW1 was sufficient to prevent alterations in the mucosa-associated microbiota. These observations, through mechanisms involving modulation of the mucosa-associated microbiota, emphasize the need of investigation of the potential clinical efficiency of such NMWs to contribute, in human beings, to a state of low inflammation in inflammatory bowel disease.

Published
2021

7. Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn’s disease

Author

Yann Guerardel, Pascal Vandekerckove, Shin-Yi Yu, Adeline Sivignon, Nathalie Ballet, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lesaffre, Gifu University, Lesaffre international, Ministere de la Recherche et de la Technologie (Universite Clermont Auvergne), Inserm (UMR 1071), INRAE (USC-2018), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lille, CNRS, Lille Neurosciences & Cognition (LilNCog) - U 1172, and Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Subjects
Male, Phosphopeptides, Polymers and Plastics, Saccharomyces cerevisiae, Mannan-glucan heteropolysaccharides, Adherent-invasive Escherichia coli, Anti-adhesive strategy, NMR analysis, Mice, Transgenic, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Bacterial Adhesion, Microbiology, Cell wall, Mannans, 03 medical and health sciences, Feces, 0302 clinical medicine, Crohn Disease, In vivo, Cell Wall, Materials Chemistry, medicine, Escherichia coli, Animals, Glucans, 030304 developmental biology, Mannan, 0303 health sciences, biology, Chemistry, Organic Chemistry, Fungal Polysaccharides, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Yeast, In vitro, 3. Good health, Anti-Bacterial Agents, Gastrointestinal Microbiome, [CHIM.POLY]Chemical Sciences/Polymers, 030211 gastroenterology & hepatology, Female, Bacteria
Abstract

International audience; The Saccharomyces cerevisiae CNCM I-3856 was previously reported to strongly inhibit adherent-invasive Escherichia coli (AIEC) adhesion to intestinal epithelial cells in vitro and to favor AIEC elimination from the gut in a murine model of Crohn's disease in vivo. In order to identify which cell wall components of yeast are responsible for AIEC elimination, constituent polysaccharides of yeast were isolated and their anti-adhesive ability against AIEC adhesion in vitro was screened. A fraction containing mannan, β-glucan and α-glucan extracted from yeast cell-walls was shown to inhibit 95% of AIEC adhesion in vitro and was thus identified as the strongest anti-adhesive yeast cell wall component. Furthermore, this mannan-glucan-containing fraction was shown to accelerate AIEC decolonization from gut in vivo. This fraction could be proposed as a treatment to eliminate AIEC bacteria in patients with Crohn's disease, a microbial trigger of intestinal inflammation.

Published
2021

8. High-Intensity interval training and α-linolenic acid supplementation improve DHA conversion and increase the abundance of gut mucosa-associated oscillospira bacteria

Author

Claire Plissonneau, Frederic Capel, Benoit Chassaing, Marine Dupuit, Florie Maillard, Ivan Wawrzyniak, Lydie Combaret, Frederic Dutheil, Monique Etienne, Guillaume Mairesse, Guillaume Chesneau, Nicolas Barnich, Nathalie Boisseau, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Société Valorex, Combourtillé, Valorex, Ministere de la Recherche et de la Technologie (M2iSH), Ministere de la Recherche et de la Technologie (AME2P Unit), Inserm (UMR 1071), INRAEINRAE (USC-2018), I-SITE project (CAP 2025) of the University of Clermont Auvergne, Kenneth Rainin Foundation, ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), European Project: ERC-2018-StG804135, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Société Valorex, Plissonneau, Claire, BOISSEAU, Nathalie, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, and Mucus-Penetrating Microbiota: Characterization, Mechanism and Therapeutic in Metabolic Disease - ERC-2018-StG804135 - INCOMING

Subjects
Blood Glucose, Erythrocytes, Docosahexaenoic Acids, MESH: physical conditioning, animal, [SDV]Life Sciences [q-bio], lcsh:TX341-641, High-Intensity Interval Training, Article, Feces, Random Allocation, Physical Conditioning, Animal, Adipocytes, microbiota, Animals, Intestinal Mucosa, Rats, Wistar, ComputingMilieux_MISCELLANEOUS, MESH: alpha-Linolenic Acid / pharmacology, MESH: clostridiales / drug effects, Clostridiales, body composition, exercise, Fatty Acids, alpha-Linolenic Acid, food and beverages, Glucose Tolerance Test, Fatty Acids, Volatile, linseed oil supplementation, Gastrointestinal Microbiome, Rats, [SDV] Life Sciences [q-bio], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, lipids (amino acids, peptides, and proteins), lcsh:Nutrition. Foods and food supply, MESH: cocosahexaenoic Acids / metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: rats, Wistar
Abstract

Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether high-intensity interval training (HIIT) and/or α-linolenic acid supplementation (to equilibrate the n-6/n-3 polyunsaturated fatty acids (PUFA) ratio) might prevent obesity disorders, particularly by modulating the mucosa-associated microbiota. Wistar rats received a low fat diet (LFD, control) or high fat diet (HFD) for 16 weeks to induce obesity. Then, animals in the HFD group were divided in four groups: HFD (control), HFD + linseed oil (LO), HFD + HIIT, HFD + HIIT + LO. In the HIIT groups, rats ran on a treadmill, 4 days.week−1. Erythrocyte n-3 PUFA content, body composition, inflammation, and intestinal mucosa-associated microbiota composition were assessed after 12 weeks. LO supplementation enhanced α-linolenic acid (ALA) to docosahexaenoic acid (DHA) conversion in erythrocytes, and HIIT potentiated this conversion. Compared with HFD, HIIT limited weight gain, fat mass accumulation, and adipocyte size, whereas LO reduced systemic inflammation. HIIT had the main effect on gut microbiota β-diversity, but the HIIT + LO association significantly increased Oscillospira relative abundance. In our conditions, HIIT had a major effect on body fat mass, whereas HIIT + LO improved ALA conversion to DHA and increased the abundance of Oscillospira bacteria in the microbiota.

Published
2021

9. When adherent-invasive E. coli plays with host glycosylation: Does it open new perspectives for therapeutic strategies in Crohn's disease?

Author

Jérémy Denizot, Nicolas Barnich, Molé, Christine, CAP 20-25 - - CAP 20-252016 - ANR-16-IDEX-0001 - IDEX - VALID, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ministere de la Recherche et de la Technologie, Inserm (UMR 1071), INRAE (USC-2018), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
MESH: Glycomics, Glycosylation, Research paper, UDP-N-acetylglucosamine (UDP-GlcNAc), lcsh:Medicine, Biology, medicine.disease_cause, MESH: Protein Glycosylation, Bacterial Adhesion, NF-κB, General Biochemistry, Genetics and Molecular Biology, Crohn's disease (CD), Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Crohn Disease, inflammatory bowel disease, MESH: Acute-Phase Reaction, Escherichia coli, medicine, Humans, MESH: Autophagy, Escherichia coli Infections, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Crohn's disease, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Crohn Disease, Crohn disease, Host (biology), MESH: Adherent Escherichia coli, lcsh:R, adherent-invasive Escherichia coli (AIEC) LF82, O-Linked β-N-acetylglucosamine (O-GlcNAc), General Medicine, medicine.disease, 3. Good health, carbohydrates (lipids), chemistry, 030220 oncology & carcinogenesis, Commentary, lcsh:Medicine (General), MESH: Celiac Disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked β-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD. Methods O-GlcNAc in intestinal epithelial tissues of CD, adherent-invasive Escherichia coli (AIEC) LF82-infected cells and mice was determined by immunoblot and immunohistochemistry. AIEC LF82 and dextran sulfate sodium were administrated into C57BL/6 mice for estabolishing inflammatory bowel disease model and for therapeutic study. Findings O-GlcNAc was increased in intestinal epithelial tissues of CD patients and AIEC LF82-infected mice. Infection of AIEC LF82 up-regulated the level of UDP-GlcNAc and increased O-GlcNAc in human colon epithelial HCT116 and HT-29 cells. We identified that IKKβ and NF-κB were O-Glycosylated in AIEC LF82-treated cells. Mutations of IKKβ (S733A) and p65 (T352A) abrogated the O-GlcNAc in IKKβ and NF-κB and inhibited AIEC LF82-induced activation of NF-κB. Application of 6-diazO-5-oxO-L-norleucine, an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAc, inactivated NF-κB in AIEC LF82-infected cells, enhanced the formation of autophagy, promoted the removal of cell-associated AIEC LF82, alleviated intestinal epithelial inflammation, and improved the survival of the colitis mice. Interpretation Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease. Funding National Natural Science Foundation of China (Nos. 81573087 and 81772924) and International Cooperation Foundation of Jilin Province (20190701006GH).

Published
2020

10. Adherent-Invasive E. coli: Update on the Lifestyle of a Troublemaker in Crohn's Disease

Author

Chervy, Mélissa, Barnich, Nicolas, Denizot, Jérémy, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ministere de la Recherche et de la Technologie, Inserm (UMR 1071), INRAe (USC-2018) Fondation pour la Recherche MedicaleECO201906008953French government IDEX-ISITE initiative of the University of Clermont Auvergne 16-IDEX-0001, and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)

Subjects
Crohn’s disease, adherent-invasive Escherichia coli, AIEC-targeting therapy, virulence gene, AIEC-host interaction, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Review, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, lcsh:Chemistry, Enteropathogenic Escherichia coli, Crohn's disease, Crohn Disease, lcsh:Biology (General), lcsh:QD1-999, Host-Pathogen Interactions, microbiota, Animals, Humans, intestinal environment, Intestinal Mucosa, lcsh:QH301-705.5
Abstract

International audience; Besides genetic polymorphisms and environmental factors, the intestinal microbiota is an important factor in the etiology of Crohn's disease (CD). Among microbiota alterations, a particular pathotype of Escherichia coli involved in the pathogenesis of CD abnormally colonizes the intestinal mucosa of patients: the adherent-invasive Escherichia coli (AIEC) pathobiont bacteria, which have the abilities to adhere to and to invade intestinal epithelial cells (IECs), as well as to survive and replicate within macrophages. AIEC have been the subject of many studies in recent years to unveil some genes linked to AIEC virulence and to understand the impact of AIEC infection on the gut and consequently their involvement in CD. In this review, we describe the lifestyle of AIEC bacteria within the intestine, from the interaction with intestinal epithelial and immune cells with an emphasis on environmental and genetic factors favoring their implantation, to their lifestyle in the intestinal lumen. Finally, we discuss AIEC-targeting strategies such as the use of FimH antagonists, bacteriophages, or antibiotics, which could constitute therapeutic options to prevent and limit AIEC colonization in CD patients.

Published
2020

11. Small-molecule inhibitors prevent the genotoxic and protumoural effects induced by colibactin-producing bacteria

Author

Tiphanie Faïs, Arlette Darfeuille-Michaud, Chiara Romagnoli, Antony Cougnoux, Gabriel Cuevas-Ramos, Richard Bonnet, Lucie Gibold, Guillaume Dalmasso, Julien Delmas, Eric Oswald, Frédéric Robin, Fabio Prati, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), CHU Clermont-Ferrand, Department of Life Sciences, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire de Technologie d'Aubière (IUT d'Aubière), Ministère de la Recherche et de la Technologie, INSERM [UMR 1071], INRA [USC-2018], Centre Hospitalier Régional Universitaire de Clermont-Ferrand, France, 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, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CHU Toulouse [Toulouse]

Subjects
0301 basic medicine, DNA damage, [SDV]Life Sciences [q-bio], ADJUVANT TREATMENT, BACTERIAL PATHOGENESIS, COLORECTAL CANCER, DRUG DEVELOPMENT, E. COLI, Biology, Ligands, medicine.disease_cause, Mice, 03 medical and health sciences, In vivo, Escherichia coli, medicine, Animals, chemistry.chemical_classification, Mice, Inbred BALB C, Ligand efficiency, Calcium-Binding Proteins, Gastroenterology, Boronic Acids, Small molecule, In vitro, 3. Good health, 030104 developmental biology, Enzyme, chemistry, Biochemistry, Docking (molecular), Polyketides, Colorectal Neoplasms, Peptides, DNA Damage, Mutagens
Abstract

International audience; Objective Colorectal cancers (CRCs) are frequently colonised by colibactin toxin-producing Escherichia coli bacteria that induce DNA damage in host cells and exhibit protumoural activities. Our objective was to identify small molecules inhibiting the toxic effects induced by these colibactin-producing bacteria. Design A structural approach was adopted for the identification of a putative ligand for the ClbP enzyme involved in the synthesis of colibactin. Intestinal epithelial cells and a CRC mouse model were used to assess the activity of the selected compounds in vitro and in vivo. Results Docking experiments identified two boron-based compounds with computed ligand efficiency values (−0.8 and −0.9 kcal/mol/atom) consistent with data expected for medicinal chemistry leads. The crystalline structure of ClbP in complex with the compounds confirmed that the compounds were binding to the active site of ClbP. The two compounds (2 mM) suppressed the genotoxic activity of colibactin-producing E coli both in vitro and in vivo. The mean degree of suppression of DNA damage for the most efficient compound was 98±2% (95% CI). This compound also prevented cell proliferation and colibactin-producing E coli-induced tumourigenesis in mice. In a CRC murine model colonised by colibactin-producing E coli, the number of tumours decreased by 3.5-fold in animals receiving the compound in drinking water (p

Published
2015

12. Impact of CDT Toxin on Human Diseases

Author

Tiphanie Faïs, Guillaume Dalmasso, Arnaud Serres, Julien Delmas, Richard Bonnet, ProdInra, Migration, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Hôpital Hôtel-Dieu de Clermont-Ferrand, CHU Clermont-Ferrand, and Ministere de la Recherche et de la Technologie, Institut national de la sante et de la recherche medicale (INSERM) UMR 1071, Institut national de la recherche agronomique (INRA) USC 2018

Subjects
0301 basic medicine, Campylobacterales, Gram-negative bacteria, Cytolethal distending toxin, Health, Toxicology and Mutagenesis, Aggregatibacter, Bacterial Toxins, lcsh:Medicine, composé organique, Review, Toxicology, CDT toxin, DNA damage, CDT-producing bacteria, Microbiology, 03 medical and health sciences, Bacterial Proteins, Risk Factors, Neoplasms, Gram-Negative Bacteria, Animals, Humans, Toxicologie, Inflammation, biology, Pasteurellaceae, lcsh:R, biology.organism_classification, Enterobacteriaceae, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, toxine, Cell Transformation, Neoplastic, 030104 developmental biology, bactérie gram négatif, physiologie cellulaire, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Host-Pathogen Interactions, Immunology, Actinobacillus, Inflammation Mediators, Gram-Negative Bacterial Infections, Haemophilus ducreyi
Abstract

International audience; Cytolethal distending toxin (CDT) is found in Gram-negative bacteria, especially in certain Proteobacteria such as the Pasteurellaceae family, including Haemophilus ducreyi and Aggregatibacter (Actinobacillus) actinomycetemcomitans, in the Enterobacteriaceae family and the Campylobacterales order, including the Campylobacter and Helicobacter species. In vitro and in vivo studies have clearly shown that this toxin has a strong effect on cellular physiology (inflammation, immune response modulation, tissue damage). Some works even suggest a potential involvement of CDT in cancers. In this review, we will discuss these different aspects.

Published
2016

13. A library of heptyl mannose-functionalized copolymers with distinct compositions, microstructures and neighboring non-sugar motifs as potent antiadhesives of type 1 piliated E. coli

Author

Julie Bouckaert, Sébastien G. Gouin, Julien Bernard, Xibo Yan, Adeline Sivignon, Etienne Fleury, Nicolas Barnich, Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Laboratoire de Synthèse Organique (Hétérochimie organique, organoéléments et matériaux) (LSOHOOM), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Matériaux Polymères - Laboratoire des Matériaux Macromoléculaires (IMP-LMM), ANR-12-BSV5-0016,STARLET,Effets thérapeutiques de polymères mannosylés synthétiques capables de contrôler les infections chroniques ntestinales à Escherichia coli en interagissant avec la dynamique de glycosylation des cellules hôtes(2012), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), French Agence Nationale de la Recherche (ANR Programme Blanc STARLET) [ANR-12-BSV5-0016-01], Ministere de la Recherche et de la Technologie, INRA (USC), Inserm (UMR 1071), Chinese Scholarship Council, Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA)

Subjects
Glycidyl methacrylate, Polymers and Plastics, Stereochemistry, INHIBITION, Mannose, Bioengineering, 02 engineering and technology, LECTIN-BINDING, 010402 general chemistry, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Ethanolamine, Polymer chemistry, Copolymer, Methacrylamide, Reversible addition−fragmentation chain-transfer polymerization, ComputingMilieux_MISCELLANEOUS, AFFINITY, ARCHITECTURE, Organic Chemistry, RAFT POLYMERIZATION, RECOGNITION, Raft, Adhesion, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, GLYCOPOLYMERS, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, CONTROLLED RADICAL POLYMERIZATION, MULTIVALENT INTERACTIONS, DENSITY, 0210 nano-technology
Abstract

International audience; A large library of mannosylated copolymers having tunable compositions, microstructures and pendant motifs neighboring mannose of distinct nature were synthesized by combining (i) sequential, batch or semi-batch RAFT (co) polymerizations of glycidyl methacrylate (GMA) and N-[7-(alpha-D-mannopyranosyloxy) heptyl] methacrylamide (HMM) and (ii) epoxy-amine post-modifications with ethanolamine, (2-amino-ethyl) trimethylammonium chloride or taurine. Examination of the anti-adhesive properties against type 1 piliated E. coli allowed for identifying copolymers among the three series of post-modified glycopolymers capable of efficiently inhibiting bacterial adhesion at 0.1 and 1 mu M (on a mannose unit basis) in pre and post-incubation adhesion assays respectively.

Published
2016

14. Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel Diseases

Author

Christophe Travelet, David Deniaud, Julien Bernard, Adeline Sivignon, Nicolas Barnich, Zhaoli Li, Etienne Fleury, Redouane Borsali, Nao Yamakawa, Arlette Darfeuille-Michaud, Agnes Crepet, Xibo Yan, Julie Bouckaert, Sébastien G. Gouin, Rostyslav Bilyy, Tetiana Dumych, Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), Ministère de la Recherche et de la Technologie, Inserm (UMR 1071) and INRA (USC-2018), ANR-12-BSV5-0016,STARLET,Effets thérapeutiques de polymères mannosylés synthétiques capables de contrôler les infections chroniques ntestinales à Escherichia coli en interagissant avec la dynamique de glycosylation des cellules hôtes(2012), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de Chimie des polymères organiques (LCPO), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Danylo Halytskiy Lviv National Medical University, Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Matériaux Polymères - Laboratoire des Matériaux Macromoléculaires (IMP-LMM), Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Synthèse Organique (Hétérochimie organique, organoéléments et matériaux) (LSOHOOM), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Recherche Agronomique (INRA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)

Subjects
Polymers and Plastics, Glycopolymer, Mannose, Bioengineering, Biology, medicine.disease_cause, Virulence factor, Microbiology, Biomaterials, chemistry.chemical_compound, Mice, Intestinal mucosa, Materials Chemistry, medicine, Cell Adhesion, Escherichia coli, [CHIM]Chemical Sciences, Animals, Humans, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, Adhesins, Escherichia coli, Polysaccharides, Bacterial, [CHIM.MATE]Chemical Sciences/Material chemistry, Inflammatory Bowel Diseases, In vitro, 3. Good health, Bacterial adhesin, [CHIM.POLY]Chemical Sciences/Polymers, Biochemistry, chemistry, Fimbriae Proteins, Ex vivo, Heptanol, HeLa Cells
Abstract

International audience; n-Heptyl alpha-D-mannose (HM) is a nanomolar antagonist of FimH, a virulence factor of E. coli. Herein we report on the construction of multivalent HM-based glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell-bacteria interactions in vitro at very low concentration (0.1 mu M on a mannose unit basis). On a valency-corrected basis, HM-based glycopolymers are, respectively, 10(2) and 10(6) times more potent than HM and D-mannose for their capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM-based glycopolymers are preserved ex vivo in the colonic loop of a transgenic mouse model of Crohns disease. All together, these results underline the promising scope of HM-based macromolecular ligands for the antiadhesive treatment of E. coli induced inflammatory bowel diseases.

Published
2015

16. Escherichia coli ClbS is a colibactin resistance protein.

Author

Bossuet-Greif N, Dubois D, Petit C, Tronnet S, Martin P, Bonnet R, Oswald E, and Nougayrède JP

Subjects
DNA Damage, Escherichia coli pathogenicity, Escherichia coli Infections microbiology, Genomic Islands, HeLa Cells, Humans, Mutagens metabolism, Peptides genetics, Virulence, Escherichia coli genetics, Escherichia coli metabolism, Peptides metabolism, Polyketide Synthases genetics, Polyketide Synthases metabolism, Polyketides metabolism
Abstract

The genomic pks island codes for the biosynthetic machinery that produces colibactin, a peptide-polyketide metabolite. Colibactin is a genotoxin that contributes to the virulence of extra-intestinal pathogenic Escherichia coli and promotes colorectal cancer. In this work, we examined whether the pks-encoded clbS gene of unknown function could participate in the self-protection of E. coli-producing colibactin. A clbS mutant was not impaired in the ability to inflict DNA damage in HeLa cells, but the bacteria activated the SOS response and ceased to replicate. This autotoxicity phenotype was markedly enhanced in a clbS uvrB double mutant inactivated for DNA repair by nucleotide excision but was suppressed in a clbS clbA double mutant unable to produce colibactin. In addition, ectopic expression of clbS protected infected HeLa cells from colibactin. Thus, ClbS is a resistance protein blocking the genotoxicity of colibactin both in the procaryotic and the eucaryotic cells., (© 2015 John Wiley & Sons Ltd.)

Published
2016
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