Multi-omics analyses unveil gut microbiota and metabolites signatures in deoxycholic acid-associated intestinal inflammation.

Objective: High-fat diet (HFD) is closely related to the increased incidence of inflammatory bowel disease (IBD), and excessive fecal deoxycholic acid (DCA) induced by HFD makes significant contribution to the colonic inflammation. However, the precise mechanisms remain unclear. This study aims to explore the association between DCA-induced alteration of gut microbiota as well as related metabolites and intestinal inflammation. Methods: Wild-type C57BL/6 J mice were orally administrated with or without 0.2% DCA for 12 weeks, then the alteration of gut microbiota signature and fecal metabolites were analyzed by metagenomic sequencing and widely-targeted metabolomics, respectively. The colonic tissue injury was confirmed by histopathological analysis and pro-inflammatory cytokines production was determined by qPCR and ELISA. Results: DCA administration induced gut microbiota dysbiosis and fecal metabolomic profile disturbance, accompanied with significantly increased expression of pro-inflammatory cytokines in intestine, including TNF- Conclusion: Our study revealed that excessive DCA led to concurrent alterations of gut microbiota and metabolites, which exhibited significant correlations with intestinal inflammation, suggesting a potential indirect regulatory pathway that may involve gut microbiota. Targeting DCA-related gut microbiota or metabolites might represent a promising intervention for HFD-associated colonic inflammation.