Investigating Intestinal Farnesoid X Receptor functions at the Intestinal Mucosal Barrier and in the Intestinal Microbiota in a Biliary Obstruction Mouse Model.

Abstract

Intestinal barrier dysfunction and dysbiosis are critical intestinal alterations in biliary obstructive diseases, for which FXR is a potential intestinal therapeutic target, but its roles and mechanisms in the intestinal tract remain poorly defined. Using gut-specific knockout mice, we demonstrate that intestinal FXR deficiency caused intestinal barrier function impairment and dysbiosis, and in a biliary obstruction model, obeticholic acid (OCA) -dependent intestinal FXR activation protected against intestinal barrier injury and dysbiosis after bile duct ligation (BDL) surgery. Furthermore, from single-cell sequencing data, FXR may directly regulate Reg3g to influence intestinal functions. In conclusion, we elucidated FXR actions in the intestine under physiological and biliary obstruction conditions, and suggest possible molecular targets which provide new insights for the intestinal treatment of biliary obstructive diseases.