title: Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases.
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.
  
  
  METHODS
  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.
authors.affiliation: INSERM ERL U 1057, UMR7203, Paris, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Duboc
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rajca
authors.forename: Dominique
authors.initials: D
authors.lastname: Rainteau
authors.forename: David
authors.initials: D
authors.lastname: Benarous
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Maubert
authors.forename: Elodie
authors.initials: E
authors.lastname: Quervain
authors.forename: Ginette
authors.initials: G
authors.lastname: Thomas
authors.forename: Véronique
authors.initials: V
authors.lastname: Barbu
authors.forename: Lydie
authors.initials: L
authors.lastname: Humbert
authors.forename: Guillaume
authors.initials: G
authors.lastname: Despras
authors.forename: Chantal
authors.initials: C
authors.lastname: Bridonneau
authors.forename: Fabien
authors.initials: F
authors.lastname: Dumetz
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grill
authors.forename: Joëlle
authors.initials: J
authors.lastname: Masliah
authors.forename: Laurent
authors.initials: L
authors.lastname: Beaugerie
authors.forename: Jacques
authors.initials: J
authors.lastname: Cosnes
authors.forename: Olivier
authors.initials: O
authors.lastname: Chazouillères
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon
authors.forename: Claude
authors.initials: C
authors.lastname: Wolf
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Mallet
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.forename: Germain
authors.initials: G
authors.lastname: Trugnan
authors.forename: Harry
authors.initials: H
authors.lastname: Sokol
authors.forename: Philippe
authors.initials: P
authors.lastname: Seksik
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000378:metabolism*; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000382:microbiology*; D054892:Metagenome; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry
chemical_list: D001647:Bile Acids and Salts