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Original article
Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases
  1. Henri Duboc1,2,3,
  2. Sylvie Rajca1,2,3,
  3. Dominique Rainteau1,2,4,
  4. David Benarous5,
  5. Marie-Anne Maubert1,2,4,
  6. Elodie Quervain1,2,
  7. Ginette Thomas1,2,4,
  8. Véronique Barbu4,
  9. Lydie Humbert1,2,4,
  10. Guillaume Despras2,
  11. Chantal Bridonneau6,
  12. Fabien Dumetz6,
  13. Jean-Pierre Grill1,2,
  14. Joëlle Masliah1,2,4,
  15. Laurent Beaugerie1,2,3,
  16. Jacques Cosnes1,2,3,
  17. Olivier Chazouillères7,
  18. Raoul Poupon7,
  19. Claude Wolf1,
  20. Jean-Maurice Mallet2,
  21. Philippe Langella6,
  22. Germain Trugnan1,2,4,
  23. Harry Sokol1,2,3,
  24. 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

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.

  • Inflammatory Bowel Disease
  • Bile Acid
  • Intestinal Microbiology
  • Inflammatory Mechanisms

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