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Article Dans Une Revue Gut Année : 2012

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

Henri Duboc
  • Fonction : Auteur
Sylvie Rajca
  • Fonction : Auteur
David Benarous
  • Fonction : Auteur
Elodie Quervain
  • Fonction : Auteur
Véronique Barbu
  • Fonction : Auteur
Lydie Humbert
  • Fonction : Auteur
Guillaume Despras
  • Fonction : Auteur
Chantal Bridonneau
  • Fonction : Auteur
Fabien Dumetz
  • Fonction : Auteur
  • PersonId : 1202992
Jean-Pierre Grill
  • Fonction : Auteur
  • PersonId : 765965
  • IdRef : 191673579
Olivier Chazouillères
  • Fonction : Auteur
Philippe Langella
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-00734237 , version 1 (21-09-2012)

Identifiants

Citer

Henri Duboc, Sylvie Rajca, Dominique Rainteau, David Benarous, Marie-Anne Maubert, et al.. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases.. Gut, 2012, 62 (4), pp.531-539. ⟨10.1136/gutjnl-2012-302578⟩. ⟨hal-00734237⟩
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