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

作者：Henri Duboc, Sylvie Rajca, Dominique Rainteau, David Benarous, Marie-Anne Maubert, Elodie Quervain, Ginette Thomas, Véronique Barbu, Lydie Humbert, Guillaume Despras, Chantal Bridonneau, Fabien Dumetz, Jean-Pierre Grill, J. Masliah, Laurent Beaugerie, Jacques Cosnes, Olivier Chazouillères, Raoul Poupon, Claude Wolf, Jean‐Maurice Mallet, Philippe Langella, Germain Trugnan, Harry Sokol, Philippe Seksik · 发表于：Gut · 年份：2012 · DOI：10.1136/gutjnl-2012-302578 · 被引用次数：940 · 研究领域：Gut microbiota and health、Drug Transport and Resistance Mechanisms、Liver Diseases and Immunity

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-i...