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Gut 62:531-539 doi:10.1136/gutjnl-2012-302578
  • Inflammatory bowel disease
  • Original article

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

  1. Philippe Seksik1,2,3
  1. 1INSERM ERL U 1057, UMR 7203, Paris, France
  2. 2UMR 7203 Laboratoire des Biomolécules, Ecole Normale Supérieure, Paris, France
  3. 3Département de Gastro-entérologie et Nutrition, Hôpital Saint Antoine, AP-HP, Paris, France
  4. 4Département de Biochimie B et LCBGM, Hôpital Saint Antoine AP-HP, Paris, France
  5. 5Mu-Tis, Paris, France
  6. 6MICA, Institut MICALIS, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, France
  7. 7Département d'Hépatologie -Centre National de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint Antoine, AP-HP, Paris, France
  1. Correspondence to Prof Philippe Seksik, Service de Gastroentérologie et Nutrition, Hôpital St-Antoine, 184 rue du Faubourg St-Antoine, 75571 Paris Cedex 12, France; philippe.seksik{at}sat.aphp.fr
  • Received 2 August 2012
  • Accepted 3 August 2012
  • Published Online First 19 September 2012

Abstract

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.