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

• Published in: Gut Vol. 62; no. 4; pp. 531 - 539
• Main Authors: Duboc, Henri, Rajca, Sylvie, Rainteau, Dominique, Benarous, David, Maubert, Marie-Anne, Quervain, Elodie, Thomas, Ginette, Barbu, Véronique, Humbert, Lydie, Despras, Guillaume, Bridonneau, Chantal, Dumetz, Fabien, Grill, Jean-Pierre, Masliah, Joëlle, Beaugerie, Laurent, Cosnes, Jacques, Chazouillères, Olivier, Poupon, Raoul, Wolf, Claude, Mallet, Jean-Maurice, Langella, Philippe, Trugnan, Germain, Sokol, Harry, Seksik, Philippe
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.04.2013; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Animals; Area Under Curve; Bacteria; Bile; Bile Acid; Bile Acids and Salts - metabolism; Biodiversity; Biosynthesis; Cell Line, Tumor; Chemical Sciences; Chi-Square Distribution; Chromatography, High Pressure Liquid; Colonic Neoplasms - pathology; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Feces - chemistry; Feces - microbiology; Homeostasis; Humans; Inflammation; Inflammatory Bowel Disease; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - microbiology; Inflammatory Mechanisms; Intestinal Microbiology; Metabolism; Metagenome; Mice; Organic chemistry; Physiology; Real-Time Polymerase Chain Reaction; Statistics, Nonparametric; Tandem Mass Spectrometry; IN-VITRO; TUMOR-NECROSIS-FACTOR; CROHNS-DISEASE; ULCERATIVE-COLITIS; FECAL MICROBIOTA; MICE; HUMAN INTESTINAL BACTERIA; LITHOCHOLIC ACID; NF-KAPPA-B; PRIMARY SCLEROSING CHOLANGITIS
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2012-302578

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.