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1. P900 A PROOF-OF-CONCEPT, PLACEBO-RANDOMIZED CONTROLLED TRIAL TARGETING ADHERENT AND INVASIVE ESCHERICHIA COLI (AIEC) WITH ANTIBIOTICS IN CROHN’S DISEASE: the TEOREM TRIAL

Author

Carbonnel, F, primary, Barnich, N, additional, Hébuterne, X, additional, Lepage, P, additional, Michiels, C, additional, Gilletta, C, additional, Wils, P, additional, Laharie, D, additional, Altwegg, R, additional, Allez, M, additional, Bouhnik, Y, additional, Agostini, H, additional, Molinari, D, additional, Ryan Balfour, S, additional, Colombel, J F, additional, Mary, J Y, additional, Walter-Petrich, A, additional, Chevret, S, additional, and Buisson, A, additional

Published
2024
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7. Role of adherent and invasive E. coli in Crohn's Disease: Lessons from the postoperative recurrence model

Author

Buisson, Anthony, Sokol, Harry, Hammoudi, Nassim, Nancey, Stéphane, Treton, Xavier, Nachury, Maria, Fumery, Mathurin, Hebuterne, Xavier, Rodrigues, Michael, Hugot, Jean-Pierre, Boschetti, Gilles, Stefanescu, Carmen, Wils, Pauline, Seksik, Philippe, Le Bourhis, Lionel, Bezault, Madeleine, Sauvanet, Pierre, Pereira, Bruno, Allez, Matthieu, Barnich, N., CHU Clermont-Ferrand, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, 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, Département de Gastroentérologie, Hôpital de l'Archet 2, Beaujon, Assistance Publique - Hôpitaux de Paris, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sorbonne Université (SU), Theraptosis S.A., Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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), 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, Service de chirurgie digestive, Hôpital Saint-André, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), DESSAIVRE, Louise, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Servcie Hépato-gastroentérolgie et Nutrition clinique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), 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 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), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Remind Study Group, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), and European Crohn’s and Colitis Organisation

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

International audience

Published
2022

9. DOP33 Role of adherent and invasive E. coli in Crohn’s Disease: Lessons from the postoperative recurrence model

Author

Buisson, A, primary, Sokol, H, additional, Hammoudi, N, additional, Nancey, S, additional, Treton, X, additional, Nachury, M, additional, Fumery, M, additional, Hébuterne, X, additional, Rodrigues, M, additional, Hugot, J P, additional, Boschetti, G, additional, Stefanescu, C, additional, Wils, P, additional, Seksik, P, additional, Le Bourhis, L, additional, Bezault, M, additional, Sauvanet, P, additional, Pereira, B, additional, Allez, M, additional, and Barnich, N, additional

Published
2022
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11. A21 ULCERATIVE COLITIS-ASSOCIATED E. COLI PATHOBIONTS POTENTIATE COLITIS IN SUSCEPTIBEL HOSTS.

Author

Yang, H, primary, Mirsepasi-Lauridsen, H, additional, Struve, C, additional, Allaire, J M, additional, Sivignon, A, additional, Vogl, W, additional, Bosman, E S, additional, Ma, C, additional, Fotovati, A, additional, Reid, G, additional, Li, X, additional, Petersen, A M, additional, Gouin, S, additional, Barnich, N, additional, Jacobson, K, additional, Yu, H, additional, Krogfelt, K, additional, and Vallance, B, additional

Published
2021
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14. Effet préventif de l’activité physique sur l’interaction tissu adipeux – microbiote intestinal chez des souris CEABAC10 exposées à la souche AIEC LF82

Author

Maillard, F., Vazeille, E., Sauvanet, P., Sirvent, P, Bonnet, R., Combaret, Lydie, Buisson, A, Chausse, P., Otero, P., Delcros, G, Chavanelle, V., Barnich, N., Boisseau, N., Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques - Clermont Auvergne (AME2P), Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine, 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hépato-Gastro Entérologie, Centre Hospitalier Universitaire de Clermont-Ferrand, Service de chirurgie digestive, Hôpital Saint-André, Department of Bacteriology, National Center for Epidemiology, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne (LAPSCO), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), 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]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-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), CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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)

Subjects
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Introduction : La maladie de crohn (MC) est une maladie inflammatoire chronique caractérisée par une modification du microbiote intestinal ainsi qu’une expansion du tissu adipeux (TA) mésentérique. Actuellement, les traitements utilisés dans la MC ne sont malheureusement pas curatifs, ont de nombreux effets secondaires et un coût prohibitif. Dans ce contexte l’activité physique (AP) pourrait être une thérapie alternative ou complémentaire, attractive et innovante via ses propriétés anti-inflammatoires, sa capacité à diminuer efficacement le TA et à moduler favorablement le microbiote intestinal. Dans ce contexte, l’objectif de cette étude était d'analyser l’impact de l’AP sur le microbiote intestinal et le TA d’un modèle murin mimant l’inflammation intestinale suite à une infection bactérienne. Matériels et Méthodes : Trente-six souris CEABAC10 mâles ont été réparties en deux groupes : l’un bénéficiant d’une roue d’activité spontanée (ROUE) et l’autre sans roue (groupe contrôle =CONT). Ces deux groupes ont été soumis à un régime « high fat/high sugar » (HF/HS) durant 12 semaines. La distance parcourue et la vitesse ont été enregistrées. La composition corporelle des animaux a été évaluée par échoMRI. Des mesures de glycémie, d’insulinémie à jeun ainsi qu’un test de tolérance au glucose ont été réalisés pour évaluer l'équilibre glycémique. A la fin des 12 semaines, les souris ont été infectées par la souche AIEC LF82, puis sacrifiées 10 jours plus tard. L’état inflammatoire a été évalué par le dosage ELISA de la lipocaline fécale et des cytokines (IL-6 et KC) au niveau adipeux et colique. La composition du microbiote intestinal associé au tissu intestinal a été analysée par séquençage de l’ADN 16S par Illumina MiSeq. Résultats : Sur les 12 semaines, le groupe ROUE a parcouru en moyenne 3,6 ± 0,4 km par jour à une vitesse moyenne de 8,5 ± 0,7 m.min-1. Le poids des animaux du groupe ROUE était plus faible de la 7ème à la 12ème semaine. La prise de masse grasse (MG) totale (en g et %) à 12 semaines était moindre dans le groupe ROUE par rapport au groupe CONT. Une corrélation négative a été mise en évidence entre la MG totale et la distance parcourue (r=-0,5 ; p 0,05). Avant l’infection, l’inflammation intestinale et l’équilibre glycémique n’étaient pas impactés par l’AP. Toutefois, la distance parcourue ou la vitesse moyenne étaient associées à une glycémie à jeun plus faible et à une meilleure tolérance au glucose (p

Published
2018

15. Comparison between faecal chitinase 3-like 1, matrix metalloprotease 9, and calprotectin to assess mucosal healing in Crohn's disease: a multicentre prospective study

Author

Buisson, A., Fumery, M., Hebuterne, X., Benjamin Pariente, Nancey, S., Quinard, R. M., Peyrin-Biroulet, L., Seksik, P., Allez, M., Lambert, C., Dupas, J. L., Filippi, J., Nachury, M., Boschetti, G., Goutte, M., Pereira, B., Bouvier, D., Bommelaer, G., Barnich, N., Vazeille, E., Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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), CHU Amiens-Picardie, Département de Gastroentérologie, Hôpital de l'Archet 2, Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de Biostatistique, CRLCC René Gauducheau, Département Gastroentérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and Institut National de la Recherche Agronomique (INRA)-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)

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

International audience

Published
2018

17. The presence of adherent-invasive Escherichia coli strains on the surgical specimen is a predictor of severe endoscopic postoperative recurrence in Crohn's disease

Author

Barnich, N., Buisson, A., Auzolle, C., Rodrigues, M., Stefanescu, C., Nancey, S., Pierre DESREUMAUX, Marteau, P., Fumery, M., Sokol, H., Treton, X., Seksik, P., Allez, M., Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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), Department of Gastroenterology, Centre Hospitalier Général Cannes, Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Beaujon, Assistance Publique - Hôpitaux de Paris, Department of Gastroenterology and Hepatology, University Medical Centre, Hôpital Claude Huriez [Lille], CHU Lille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP, Hôpital Lariboisière, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), European Crohn's and Colitis Organisation, Université de Lille, Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

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

International audience

Published
2017

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

Author

Dalmasso Guillaume, Beyrouthy Racha, Brugiroux Sandrine, Ruppé Etienne, Guillouard Laurent, Bonnin Virginie, Saint-Sardos Pierre, Ghozlane Amine, Gaumet Vincent, Barnich Nicolas, Delmas Julien, and Bonnet Richard

Subjects
mcr-1, Colistin, Antibiotic resistance, Antimicrobial peptides, Virulence, Inflammation, Microbial ecology, QR100-130
Abstract

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. Video Abstract

Published
2023
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21. P144 Comparison between faecal chitinase 3-like 1, matrix metalloprotease 9, and calprotectin to assess mucosal healing in Crohn’s disease: a multicentre prospective study

Author

Buisson, A, primary, Fumery, M, additional, Hébuterne, X, additional, Pariente, B, additional, Nancey, S, additional, Minet Quinard, R, additional, Peyrin-Biroulet, L, additional, Seksik, P, additional, Allez, M, additional, Lambert, C, additional, Dupas, J -L, additional, Filippi, J, additional, Nachury, M, additional, Boschetti, G, additional, Goutte, M, additional, Pereira, B, additional, Bouvier, D, additional, Bommelaer, G, additional, Barnich, N, additional, and Vazeille, E, additional

Published
2018
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23. Impact of intestinal dysbiosis on mouse models of colonic hypersensitivity

Author

Carvalho, F., Lashermes, A., Miquel, S., Martin Rosique, Rebeca, Gelor, A., Barnich, N., Eschalier, A., Ardid, D., Thomas, Muriel, Langella, Philippe, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Neuro-Dol - Clermont Auvergne (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-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), Neuro-Dol - Clermont Auvergne ( Neuro-Dol ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne ( LMGE ), Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne ( M2iSH ), and Université Clermont Auvergne ( UCA )

Subjects
[ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], digestive system diseases
Abstract

Impact of intestinal dysbiosis on mouse models of colonic hypersensitivity. NeuroGASTRO 2015

Published
2015

24. Predictors of post-operative endoscopic recurrence in Crohn's disease: a prospective study of the REMIND group

Author

Allez, Matthieu, Stefanescu, Carmen, Nancey, Stéphane, Buisson, Anthony, Desreumaux, Pierre, Marteau, Philippe, Fumery, Mathurin, Baudry, Clotilde, Filippi, Jérôme, Sokol, Harry, Barnich, N., Hofman, P., Treton, Xavier, Seksik, Philippe, Grp, Remind Study, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, CHU Lille, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], 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, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), 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), and European Crohn's and Colitis Organisation

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

International audience

Published
2015
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26. Monocyte-derived Macrophages from Crohn's Disease Patients Are Impaired in the Ability to Control Intracellular Adherent-Invasive Escherichia coli and Exhibit Disordered Cytokine Secretion Profile

Author

Vazeille, E., primary, Buisson, A., additional, Bringer, M.-A., additional, Goutte, M., additional, Ouchchane, L., additional, Hugot, J.-P., additional, de Vallee, A., additional, Barnich, N., additional, Bommelaer, G., additional, and Darfeuille-Michaud, A., additional

Published
2015
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28. Induction of mu opioid and cannabinoid receptors by probiotics

Author

Rousseaux, C., Thuru, Xavier, Gelot, A., Barnich, N., Neut, C., Dubuquoy, C, Ouwehand, A, Ardid, D., Carcano, D, Desreumaux, P., DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-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), Université catholique de Lille (UCL), Pharmacologie fondamentale et clinique de la douleur, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Claude Huriez, and Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
[SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

36. Adherent invasive Escherichia coli strains from patients with Crohn's disease survive and replicate within macrophages without inducing host cell death.

Author

Glasser, A L, Boudeau, J, Barnich, N, Perruchot, M H, Colombel, J F, and Darfeuille-Michaud, A

Abstract

Escherichia coli strains recovered from Crohn's disease (CD) lesions are able to adhere to and invade cultured intestinal epithelial cells. We analyzed the behavior within macrophages of adherent invasive E. coli (AIEC) strains isolated from patients with CD. All the 15 AIEC strains tested were able to replicate extensively within J774-A1 cells: the numbers of intracellular bacteria increased 2.2- to 74.2-fold at 48 h over that at 1 h postinfection. By use of murine peritoneal macrophages and human monocyte-derived-macrophages, the reference AIEC strain LF82 was confirmed to be able to survive intracellularly. Transmission electron micrographs of AIEC LF82-infected macrophages showed that at 24 h postinfection, infected cells harbored large vacuoles containing numerous bacteria, as a result of the fusion of several vacuoles occurring after 8 h postinfection. No lactate dehydrogenase (LDH) release, no sign of DNA fragmentation or degradation, and no binding to fluorescein isothlocyanate-labeled annexin V were observed with LF82-infected J774-A1 cells, even after 24 h postinfection. LF82-infected J774-A1 cells secreted 2.7-fold more tumor necrosis factor alpha (TNF-alpha) than cells stimulated with 1 microg of lipopolysaccharide (LPS)/ml. No release of interleukin-1beta was observed with LPS-prestimulated J774-A1 cells infected with AIEC LF82. These findings showed that (i) AIEC strains are able to survive and to replicate within macrophages, (ii) AIEC LF82 replication does not induce any cell death of the infected cells, and (iii) LF82-infected J774-A1 cells release high levels of TNF-alpha. These properties could be related to some features of CD and particularly to granuloma formation, one of the hallmarks of CD lesions.

Published
2001

38. T cell clonal expansions in ileal Crohn's disease are associated with smoking behaviour and postoperative recurrence

Author

Allez, M, primary, Auzolle, C, additional, Ngollo, M, additional, Bottois, H, additional, Chardiny, V, additional, Corraliza, AM, additional, Salas, A, additional, Perez, K, additional, Stefanescu, C, additional, Nancey, S, additional, Buisson, A, additional, Pariente, B, additional, Fumery, M, additional, Sokol, H, additional, Tréton, X, additional, Barnich, N, additional, Seksik, P, additional, and Le Bourhis, L, additional

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41. ATG16L1 in myeloid cells limits colorectal tumor growth in Apc Min/+ mice infected with colibactin-producing Escherichia coli via decreasing inflammasome activation.

Author

Salesse L, Duval A, Sauvanet P, Da Silva A, Barnich N, Godfraind C, Dalmasso G, and Nguyen HTT

Subjects
Animals, Mice, Autophagy genetics, Escherichia coli Infections immunology, Escherichia coli Infections microbiology, Escherichia coli Infections pathology, Escherichia coli Infections metabolism, Mice, Inbred C57BL, Adenomatous Polyposis Coli Protein genetics, Adenomatous Polyposis Coli Protein metabolism, Cell Proliferation, Tumor Microenvironment immunology, Polyketides metabolism, Colorectal Neoplasms microbiology, Colorectal Neoplasms pathology, Colorectal Neoplasms metabolism, Colorectal Neoplasms immunology, Colorectal Neoplasms genetics, Inflammasomes metabolism, Peptides metabolism, Myeloid Cells metabolism, Autophagy-Related Proteins metabolism, Autophagy-Related Proteins genetics, Escherichia coli
Abstract

Escherichia coli strains producing the genotoxin colibactin, designated as CoPEC (colibactin-producing E. coli ), have emerged as an important player in the etiology of colorectal cancer (CRC). Here, we investigated the role of macroautophagy/autophagy in myeloid cells, an important component of the tumor microenvironment, in the tumorigenesis of a susceptible mouse model infected with CoPEC. For that, a preclinical mouse model of CRC, the Apc Min/+ mice, with Atg16l1 deficiency specifically in myeloid cells ( Apc Min/+ / Atg16l1[∆MC] ) and the corresponding control mice ( Apc Min/+ ), were infected with a clinical CoPEC strain 11G5 or its isogenic mutant 11G5 ∆clbQ that does not produce colibactin. We showed that myeloid cell-specific Atg16l1 deficiency led to an increase in the volume of colonic tumors in Apc Min/+ mice under infection with 11G5, but not with 11G5 ∆clbQ . This was accompanied by increased colonocyte proliferation, enhanced inflammasome activation and IL1B/IL-1β secretion, increased neutrophil number and decreased total T cell and cytotoxic CD8 + T cell numbers in the colonic mucosa and tumors. In bone marrow-derived macrophages (BMDMs), compared to uninfected and 11G5∆ clbQ -infected conditions, 11G5 infection increased inflammasome activation and IL1B secretion, and this was further enhanced by autophagy deficiency. These data indicate that ATG16L1 in myeloid cells was necessary to inhibit colonic tumor growth in CoPEC-infected Apc Min/+ mice via inhibiting colibactin-induced inflammasome activation and modulating immune cell response in the tumor microenvironment. Abbreviation : AOM, azoxymethane; APC, APC regulator of WNT signaling pathway; ATG, autophagy related; Atg16l1[∆MC] mice, mice deficient for Atg16l1 specifically in myeloid cells; CASP1, caspase 1; BMDM, bone marrow-derived macrophage; CFU, colony-forming unit; CoPEC, colibactin-producing Escherichia coli ; CRC, colorectal cancer; CXCL1/KC, C-X-C motif chemokine ligand 1; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; MC, myeloid cell; MOI, multiplicity of infection; PBS, phosphate-buffered saline; pks , polyketide synthase; qRT-PCR, quantitative real-time reverse-transcription polymerase chain reaction; siRNA, small interfering RNA; TME, tumor microenvironment; TNF/TNF-α, tumor necrosis factor.

Published
2024
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42. Increased levels of anti-Encephalitozoon intestinalis antibodies in patients with colorectal cancer.

Author

Nourrisson C, Moniot M, Vercruysse L, Bonnin V, Pereira B, Barnich N, Bonnet M, Jary M, Pezet D, Gagnière J, and Poirier P

Subjects
Humans, Male, Female, Middle Aged, Aged, Seroepidemiologic Studies, Enzyme-Linked Immunosorbent Assay, Adult, Immunoglobulin G blood, Aged, 80 and over, Immunoglobulin A blood, Colorectal Neoplasms immunology, Colorectal Neoplasms microbiology, Antibodies, Fungal blood, Encephalitozoon immunology, Encephalitozoonosis epidemiology, Encephalitozoonosis immunology, Encephalitozoonosis microbiology
Abstract

Background: The prevalence of microsporidiosis in the general population, or within specific groups of individuals/patients, is largely underestimated. The absence of specific seroprevalence tools limits knowledge of the epidemiology of these opportunistic pathogens, although known since the 1980s. Since microsporidia hijack the machinery of its host cell and certain species multiply within intestinal cells, a potential link between the parasite and colorectal cancer (CRC) has been suggested., Methodology/principal Findings: To explore a potential epidemiological link between microsporidia and CRC, we evaluated the seroprevalence of Encephalitozoon intestinalis among CRC patients and healthy subjects using ELISA assays based on two recombinant proteins, namely rEiPTP1 and rEiSWP1, targeting polar tube and spore wall proteins. ELISA were performed in 141 CRC patients and 135 healthy controls. Patients with CRC had significantly higher anti-rEiPTP1 IgG levels than subjects in the control group. Anti-rEiPTP1 IgG, anti-rEiSWP1 IgG and anti-rEiPTP1 IgA levels were significantly increased among men with CRC compared to healthy men. Women with CRC who had died had higher rEiSWP1 IgG levels than those who were still alive., Conclusions/significance: These higher antibody levels against microsporidia in patients with CRC suggest a relationship between microsporidia and pathophysiology of CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nourrisson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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43. Preclinical and clinical evidence of the association of colibactin-producing Escherichia coli with anxiety and depression in colon cancer.

Author

Rondepierre F, Meynier M, Gagniere J, Deneuvy V, Deneuvy A, Roche G, Baudu E, Pereira B, Bonnet R, Barnich N, Carvalho FA, Pezet D, Bonnet M, and Jalenques I

Subjects
Animals, Humans, Male, Mice, Female, Aged, Middle Aged, Escherichia coli isolation & purification, Colonic Neoplasms psychology, Colonic Neoplasms microbiology, Prevalence, Brain-Gut Axis, Mice, Inbred C57BL, Polyketides metabolism, Depression psychology, Depression microbiology, Gastrointestinal Microbiome, Anxiety psychology, Anxiety microbiology, Anxiety etiology, Escherichia coli Infections psychology, Escherichia coli Infections microbiology, Disease Models, Animal, Peptides metabolism
Abstract

Background: The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing Escherichia coli (CoPEC)., Aim: To evaluate the association between CoPEC prevalence and anxiety- and depressive-like behaviors with both preclinical and clinical approaches., Methods: Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview. Results were compared according to the CoPEC colonization. In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain. Their behavior was assessed using the Elevated Plus Maze test, the Forced Swimming Test and the Behavior recognition system PhenoTyper ® ., Results: In a limited cohort, all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis, whereas only one patient (17%) without CoPEC did. This result was confirmed in C57BL6/J wild-type mice and in a CRC susceptibility mouse model (adenomatous polyposis coli multiple intestinal neoplasia/+ ). Mice exhibited a significant increase in anxiety- and depressive-like behaviors after chronic infection with a CoPEC strain., Conclusion: This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties., Competing Interests: Conflict-of-interest statement: Pr. Bonnet has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Published
2024
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44. Effects of a Cycling versus Running HIIT Program on Fat Mass Loss and Gut Microbiota Composition in Men with Overweight/Obesity.

Author

Couvert A, Goumy L, Maillard F, Esbrat A, Lanchais K, Saugrain C, Verdier C, Doré E, Chevarin C, Adjtoutah D, Morel C, Pereira B, Martin V, Lancha AH Jr, Barnich N, Chassaing B, Rance M, and Boisseau N

Subjects
Adult, Humans, Male, Middle Aged, Bicycling, Body Composition physiology, Obesity therapy, Overweight therapy, RNA, Ribosomal, 16S, Gastrointestinal Microbiome, High-Intensity Interval Training, Running
Abstract

Purpose: High-intensity interval training (HIIT) can efficiently decrease total and (intra-)abdominal fat mass (FM); however, the effects of running versus cycling HIIT programs on FM reduction have not been compared yet. In addition, the link between HIIT-induced FM reduction and gut microbiota must be better investigated. The aim of this study was to compare the effects of two 12-wk HIIT isoenergetic programs (cycling vs running) on body composition and fecal microbiota composition in nondieting men with overweight or obesity., Methods: Sixteen men (age, 54.2 ± 9.6 yr; body mass index, 29.9 ± 2.3 kg·m -2 ) were randomly assigned to the HIIT-BIKE (10 × 45 s at 80%-85% of maximal heart rate, 90-s active recovery) or HIIT-RUN (9 × 45 s at 80%-85% of maximal heart rate, 90-s active recovery) group (3 times per week). Dual-energy x-ray absorptiometry was used to determine body composition. Preintervention and postintervention fecal microbiota composition was analyzed by 16S rRNA gene sequencing, and diet was controlled., Results: Overall, body weight, and abdominal and visceral FM decreased over time ( P < 0.05). No difference was observed for weight, total body FM, and visceral FM between groups (% change). Conversely, abdominal FM loss was greater in the HIIT-RUN group (-16.1% vs -8.3%; P = 0.050). The α-diversity of gut microbiota did not vary between baseline and intervention end and between groups, but was associated with abdominal FM change ( r = -0.6; P = 0.02). The baseline microbiota profile and composition changes were correlated with total and abdominal/visceral FM losses., Conclusions: Both cycling and running isoenergetic HIIT programs improved body composition in men with overweight/obesity. Baseline intestinal microbiota composition and its postintervention variations were correlated with FM reduction, strengthening the possible link between these parameters. The mechanisms underlying the greater abdominal FM loss in the HIIT-RUN group require additional investigations., (Copyright © 2024 by the American College of Sports Medicine.)

Published
2024
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45. Identification of autophagy receptors for the Crohn's disease-associated adherent-invasive Escherichia coli .

Author

Da Silva A, Dalmasso G, Larabi A, Hoang MHT, Billard E, Barnich N, and Nguyen HTT

Subjects
Humans, HeLa Cells, Intestinal Mucosa metabolism, Carrier Proteins metabolism, Escherichia coli genetics, Escherichia coli metabolism, Autophagy physiology, Cytokines metabolism, Bacterial Adhesion, Crohn Disease, Escherichia coli Infections metabolism
Abstract

Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key process for the maintenance of cellular homeostasis, which allows the degradation of damaged cytoplasmic components and pathogens via lysosome. We have shown that a functional autophagy is necessary for AIEC clearance. Here, we aimed at identifying the autophagy receptor(s) responsible to target AIEC to autophagy for degradation., Methods: The levels of autophagy receptors p62, NDP52, NBR1, TAX1BP1 and Optineurin were knocked down in human intestinal epithelial cells T84 using siRNAs. The NDP52 knock-out (KO) and p62 KO HeLa cells, as well as NDP52 KO HeLa cells expressing the wild-type NDP52 or the mutated NDP52 Val248Ala protein were used., Results and Discussion: We showed that, among the tested autophagy receptors (p62, NDP52, NBR1, TAX1BP1 and Optineurin), diminished expression of p62 or NDP52 increased the number of the clinical AIEC LF82 strain inside epithelial cells. This was associated with increased pro-inflammatory cytokine production. Moreover, p62 or NDP52 directly colocalized with AIEC LF82 and LC3, an autophagy marker. As the NDP52 Val248Ala polymorphism has been associated with increased CD susceptibility, we investigated its impact on AIEC control. However, in HeLa cell and under our experimental condition, no effect of this polymorphism neither on AIEC LF82 intracellular number nor on pro-inflammatory cytokine production was observed. Together, our results suggest that p62 and NDP52 act as autophagy receptors for AIEC recognition, controlling AIEC intracellular replication and inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NR declared a past co-authorship with the author NB to the handling editor., (Copyright © 2024 Da Silva, Dalmasso, Larabi, Hoang, Billard, Barnich and Nguyen.)

Published
2024
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47. ChiA: a major player in the virulence of Crohn's disease-associated adherent and invasive Escherichia coli (AIEC).

Author

Fargeas M, Faure F, Douadi C, Chevarin C, Birer A, Sivignon A, Rodrigues M, Denizot J, Billard E, Barnich N, and Buisson A

Subjects
Humans, Animals, Mice, Virulence, Disease Models, Animal, Adhesins, Escherichia coli metabolism, Adhesins, Escherichia coli genetics, Female, Male, Colitis microbiology, Colitis pathology, Virulence Factors genetics, Virulence Factors metabolism, Mice, Inbred C57BL, Mucins metabolism, Crohn Disease microbiology, Crohn Disease pathology, Escherichia coli genetics, Escherichia coli pathogenicity, Escherichia coli metabolism, Bacterial Adhesion, Intestinal Mucosa microbiology, Intestinal Mucosa metabolism, Intestinal Mucosa pathology, Escherichia coli Infections microbiology
Abstract

We investigated the role of ChiA and its associated polymorphisms in the interaction between Crohn's disease (CD)-associated adherent-invasive Escherichia coli (AIEC) and intestinal mucosa. We observed a higher abundance of chiA among the metagenome of CD patients compared to healthy subjects. In dextran sulfate sodium-induced colitis mice model, AIEC-LF82∆ chiA colonization was reduced in ileal, colonic and fecal samples compared to wild-type LF82. The binding of ChiA to recombinant human CHI3L1 or mucus was higher with the pathogenic polymorphism. The strength of ChiA-mucin interaction was 300-fold stronger than ChiA-rhCHI3L1. ChiA was able to degrade mucin to promote its growth and enabled LF82 to get closer to epithelial cells. The pathogenic polymorphism of ChiA had a stronger impact on mucus degradation than on the binding capability of AIEC to adhere to the intestinal epithelium. We observed that ChiA could favor an efficient bacterial invasion of intestinal crypts, and that ChiA, especially its pathogenic polymorphism, gives LF82 an advantage to uptake within Peyer's patches, macrophages and mesenteric lymph nodes. All together, these data support the role of ChiA in the virulence of AIEC and show that it could be a promising target to reduce AIEC colonization in patients with CD.

Published
2024
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48. The colibactin-producing Escherichia coli alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance.

Author

de Oliveira Alves N, Dalmasso G, Nikitina D, Vaysse A, Ruez R, Ledoux L, Pedron T, Bergsten E, Boulard O, Autier L, Allam S, Motreff L, Sauvanet P, Letourneur D, Kashyap P, Gagnière J, Pezet D, Godfraind C, Salzet M, Lemichez E, Bonnet M, Najjar I, Malabat C, Monot M, Mestivier D, Barnich N, Yadav P, Fournier I, Kennedy S, Mettouchi A, Bonnet R, Sobhani I, and Chamaillard M

Subjects
Humans, Escherichia coli genetics, Escherichia coli metabolism, Tumor Microenvironment, Drug Resistance, Neoplasm, Mutagens metabolism, Neoplasm Recurrence, Local, Lipids, Gastrointestinal Microbiome, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms microbiology, Polyketides metabolism, Peptides
Abstract

Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8 + T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land's cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5 ∆ClbQ ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.

Published
2024
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49. AIEC-dependent pathogenic Th17 cell transdifferentiation in Crohn's disease is suppressed by rfaP and ybaT deletion.

Author

Leccese G, Chiara M, Dusetti I, Noviello D, Billard E, Bibi A, Conte G, Consolandi C, Vecchi M, Conte MP, Barnich N, Caprioli F, Facciotti F, and Paroni M

Subjects
Humans, Escherichia coli Proteins genetics, Escherichia coli Proteins metabolism, Gene Deletion, Interferon-gamma metabolism, Interferon-gamma genetics, Interferon-gamma immunology, Virulence Factors genetics, Virulence Factors metabolism, Th17 Cells immunology, Crohn Disease immunology, Crohn Disease genetics, Cell Transdifferentiation genetics, Dendritic Cells immunology, Interleukin-23 genetics, Interleukin-23 metabolism, Interleukin-23 immunology, Escherichia coli genetics, Escherichia coli immunology
Abstract

Mucosal enrichment of the Adherent-Invasive E. coli (AIEC) pathotype and the expansion of pathogenic IFNγ-producing Th17 (pTh17) cells have been linked to Crohn's Disease (CD) pathogenesis. However, the molecular pathways underlying the AIEC-dependent pTh17 cell transdifferentiation in CD patients remain elusive. To this aim, we created and functionally screened a transposon AIEC mutant library of 10.058 mutants to identify the virulence determinants directly implicated in triggering IL-23 production and pTh17 cell generation. pTh17 cell transdifferentiation was assessed in functional assays by co-culturing AIEC-infected human dendritic cells (DCs) with autologous conventional Th17 (cTh17) cells isolated from blood of Healthy Donors (HD) or CD patients. AIEC triggered IL-23 hypersecretion and transdifferentiation of cTh17 into pTh17 cells selectively through the interaction with CD-derived DCs. Moreover, the chronic release of IL-23 by AIEC-colonized DCs required a continuous IL-23 neutralization to significantly reduce the AIEC-dependent pTh17 cell differentiation. The multi-step screenings of the AIEC mutant's library revealed that deletion of ybaT or rfaP efficiently hinder the IL-23 hypersecretion and hampered the AIEC-dependent skewing of protective cTh17 into pathogenic IFNγ-producing pTh17 cells. Overall, our findings indicate that ybaT (inner membrane transport protein) and rfaP (LPS-core heptose kinase) represent novel and attractive candidate targets to prevent chronic intestinal inflammation in CD.

Published
2024
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50. Colibactin-producing Escherichia coli enhance resistance to chemotherapeutic drugs by promoting epithelial to mesenchymal transition and cancer stem cell emergence.

Author

Dalmasso G, Cougnoux A, Faïs T, Bonnin V, Mottet-Auselo B, Nguyen HT, Sauvanet P, Barnich N, Jary M, Pezet D, Delmas J, and Bonnet R

Subjects
Humans, Mice, Animals, Escherichia coli genetics, Escherichia coli metabolism, Epithelial-Mesenchymal Transition, Mutagens metabolism, Disease Models, Animal, Neoplastic Stem Cells metabolism, Gastrointestinal Microbiome, Polyketides pharmacology, Polyketides metabolism, Neoplasms, Peptides
Abstract

Human colorectal cancers (CRCs) are readily colonized by colibactin-producing E. coli (CoPEC). CoPEC induces DNA double-strand breaks, DNA mutations, genomic instability, and cellular senescence. Infected cells produce a senescence-associated secretory phenotype (SASP), which is involved in the increase in tumorigenesis observed in CRC mouse models infected with CoPEC. This study investigated whether CoPEC, and the SASP derived from CoPEC-infected cells, impacted chemotherapeutic resistance. Human intestinal epithelial cells were infected with the CoPEC clinical 11G5 strain or with its isogenic mutant, which is unable to produce colibactin. Chemotherapeutic resistance was assessed in vitro and in a xenograft mouse model. Expressions of cancer stem cell (CSC) markers in infected cells were investigated. Data were validated using a CRC mouse model and human clinical samples. Both 11G5-infected cells, and uninfected cells incubated with the SASP produced by 11G5-infected cells exhibited an increased resistance to chemotherapeutic drugs in vitro and in vivo . This finding correlated with the induction of the epithelial to mesenchymal transition (EMT), which led to the emergence of cells exhibiting CSC features. They grew on ultra-low attachment plates, formed colonies in soft agar, and overexpressed several CSC markers (e.g. CD133, OCT-3/4, and NANOG). In agreement with these results, murine and human CRC biopsies colonized with CoPEC exhibited higher expression levels of OCT-3/4 and NANOG than biopsies devoid of CoPEC. Conclusion : CoPEC might aggravate CRCs by inducing the emergence of cancer stem cells that are highly resistant to chemotherapy.

Published
2024
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