1. Fatty acids produced by the gut microbiota dampen host inflammatory responses by modulating intestinal SUMOylation
- Author
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Chaima Ezzine, Léa Loison, Nadine Montbrion, Christine Bôle-Feysot, Pierre Déchelotte, Moïse Coëffier, David Ribet, Ribet, David, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de nutrition [CHU Rouen], CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
- Subjects
Microbiology (medical) ,Gut microbiota ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,host-bacteria interactions ,Microbiology ,Branched Chain Fatty Acids (BCFAs) ,Ubiquitin-like proteins ,intestinal inflammation ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,post-translational modifications ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Inflammation ,Short Chain Fatty Acids (SCFAs) ,Bacteria ,Microbiota ,Fatty Acids ,Gastroenterology ,Sumoylation ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Fatty Acids, Volatile ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Gastrointestinal Microbiome ,Intestines ,Infectious Diseases ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology - Abstract
International audience; The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. The effect of gut commensal bacteria on host protein SUMOylation, an essential ubiquitin-like modification involved in various intestinal functions, remains, however, unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in intestinal cells in a pH-dependent manner. We demonstrate that these metabolites inactivate intestinal deSUMOylases and promote the hyperSUMOylation of nuclear matrix-associated proteins. We further show that BCFAs inhibit the NF-κB pathway, decrease pro-inflammatory cytokine expression, and promote intestinal epithelial integrity. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses triggered by the gut microbiota.
- Published
- 2022
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