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Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases

Henri DubocHôpital Saint-AntoineSylvie RajcaDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, FranceDominique RainteauLaboratoire des BiomoléculesDavid BenarousMarie-Anne MaubertINSERM ERL U 1057, UMR 7203, Paris, FranceElodie QuervainUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceGinette ThomasDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceVéronique BarbuDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceLydie HumbertHôpital Saint-AntoineGuillaume DesprasUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceChantal BridonneauMICA, Institut MICALIS, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, FranceFabien DumetzMICA, Institut MICALIS, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, FranceJean-Pierre GrillUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceJ. MasliahUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceLaurent BeaugerieUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceJacques CosnesUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceOlivier ChazouillèresDépartement d'Hépatologie -Centre National de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint Antoine, AP-HP, Paris, FranceRaoul PouponAssistance Publique – Hôpitaux de ParisClaude WolfLaboratoire des BiomoléculesJean‐Maurice MalletUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FrancePhilippe LangellaMICA, Institut MICALIS, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, FranceGermain TrugnanUMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, FranceHarry SokolHôpital Saint-AntoinePhilippe SeksikINSERM ERL U 1057, UMR 7203, Paris, France

2012en

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ABI

Annotatsiya

OBJECTIVE: Gut microbiota metabolises bile acids (BA). As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the impact of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial cell inflammation response. DESIGN: Faecal and serum BA rates, expressed as a proportion of total BA, were assessed by high-performance liquid chromatography tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29). The faecal microbiota composition was assessed by quantitative real-time PCR. Using BA profiles and microbiota composition, cluster formation between groups was generated by ranking models. The faecal BA profiles in germ-free and conventional mice were compared. Direct enzymatic activities of BA biotransformation were measured in faeces. The impact of BA on the inflammatory response was investigated in vitro using Caco-2 cells stimulated by IL-1β. RESULTS: IBD-associated dysbiosis was characterised by a decrease in the ratio between Faecalibacterium prausntizii and Escherichia coli. Faecal-conjugated BA rates were significantly higher in active IBD, whereas, secondary BA rates were significantly lower. Interestingly, active IBD patients exhibited higher levels of faecal 3-OH-sulphated BA. The deconjugation, transformation and desulphation activities of the microbiota were impaired in IBD patients. In vitro, secondary BA exerted anti-inflammatory effects, but sulphation of secondary BAs abolished their anti-inflammatory properties. CONCLUSIONS: Impaired microbiota enzymatic activity observed in IBD-associated dysbiosis leads to modifications in the luminal BA pool composition. Altered BA transformation in the gut lumen can erase the anti-inflammatory effects of some BA species on gut epithelial cells and could participate in the chronic inflammation loop of IBD.

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DOI: 10.1136/gutjnl-2012-302578

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