Modulation of the Gut Microbiota-farnesoid X Receptor Axis Improves Deoxycholic Acid-induced Intestinal Inflammation in Mice

Background and Aims: Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernised diet is implicated in the pathogenesis of IBD.The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation. Methods: Wild-type C57BL mice, 4 weeks old, were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail, for 24 weeks. Histopathology, western blotting, and qPCR were performed on the intestinal tissue. Faecal microbiota was analysed by 16S rDNA sequencing. Faecal bile acid and short chain 0 fatty acid (SCFA) levels were analysed by chromatography. Results: Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated fibroblast growth factor 15, and normalised bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA. Conclusions: DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid profiles. Interventions targeting the gut microbiota-FXR signalling pathway may reduce DCA-induced intestinal disease.

Automated summary

The study revealed that DCA-induced intestinal inflammation is associated with dysbiosis of gut microbiota and alterations in bile acid profiles. Administration of fexaramine can alleviate DCA-induced intestinal injury, increase the abundance of SCFA-producing bacteria, and reduce the occurrence of intestinal diseases.