Статья

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

Henri DubocDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, FranceSylvie RajcaDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, FranceDominique RainteauDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceDavid BenarousMarie-Anne MaubertDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceElodie QuervainINSERM ERL U 1057, UMR 7203, Paris, FranceGinette ThomasDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceVéronique BarbuHôpital Saint-AntoineLydie HumbertDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceGuillaume 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 GrillINSERM ERL U 1057, UMR 7203, Paris, FranceJ. MasliahDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceLaurent BeaugerieDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, FranceJacques CosnesDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, FranceOlivier ChazouillèresDépartement d'Hépatologie -Centre National de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint Antoine, AP-HP, Paris, FranceRaoul PouponDépartement d'Hépatologie -Centre National de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint Antoine, AP-HP, Paris, FranceClaude WolfINSERM ERL U 1057, UMR 7203, Paris, FranceJean‐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 TrugnanDépartement de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, FranceHarry SokolDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, FrancePhilippe SeksikDépartement de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, France

2012en

ABI

Аннотация

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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Идентификаторы

DOI: 10.1136/gutjnl-2012-302578

Цитирования и источники

Цитирований: 2Использованных источников: 0

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