Enterohepatic Axis Reprogramming via S1PR2 Inhibition Activates Compensatory Microbiota-Bile Acid Crosstalk to Ameliorate Colitis

Studies have revealed that gut microbiota dysbiosis and bile acid metabolism play pivotal roles in the pathogenesis of inflammatory bowel disease, and there exists a reciprocal interaction between gut microbiota and bile acid metabolism. S1PR2, a G protein-coupled receptor, has been demonstrated to exert pro-inflammatory effects in various diseases. Our findings indicate that the S1PR2 inhibitor JTE-013 ameliorates intestinal inflammation in mice with DSS-induced colitis. However, the precise mechanisms involved remain unclear. Therefore, this study investigates whether JTE-013 ameliorates murine colitis through modulation of the gut microbiota-bile acid metabolism axis.