Henri Duboc

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.

BACKGROUND: Irritable bowel syndrome (IBS) is a multifactorial disease for which a dysbiosis of the gut microbiota has been described. Bile acids (BA) could play a role as they are endogenous laxatives and are metabolized by gut microbiota. We compared fecal BA profiles and microbiota in healthy subjects (HS) and patients with diarrhea-predominant IBS (IBS-D), and we searched for an association with symptoms. METHODS: Clinical features and stool samples were collected in IBS-D patients and HS. Fecal BA profiles were generated using HPLC coupled to tandem mass spectrometry. The fecal microbiota composition was assessed by q-PCR targeting dominant bacterial groups and species implicated in BA transformation. KEY RESULTS: Fourteen IBS-D patients and 18 HS were included. The two groups were comparable in terms of age and sex. The percentage of fecal primary BA was significantly higher in IBS-D patients than in HS, and it was significantly correlated with stool consistency and frequency. Fecal counts of all bacteria, lactobacillus, coccoides, leptum and Faecalibacterium prausnitzii were similar. There was a significant increase of Escherichia coli and a significant decrease of leptum and bifidobacterium in IBS-D patients. CONCLUSIONS & INFERENCES: We report an increase of primary BA in the feces of IBS-D patients compared to HS, correlated with stool consistency and frequency. A dysbiosis of different bacterial groups was detected, some of them involved in BA transformation. As the gut microbiota is the exclusive pathway to transform primary into secondary BA, this suggests a functional consequence of dysbiosis, leading to lower BA transformation.