Odoribacter laneus protects intestinal barrier by bile acid-FXR axis in acute pancreatitis

Odoribacter laneus (O. laneus) is a promising probiotic. Acute pancreatitis (AP) is an acute abodominal disease accompanied by intestinal barrier dysfunction and gut dysbiosis. However, the effects of O. laneus in AP remain unexplored. We established AP model of C57BL/6 mice. Western blotting and immunohistofluorescence were used to detect the expression of intestinal tight junction proteins and FXR/NLRP3 pathway. The changes of gut microbiota and bile acids (BAs) were analyzed by 16 S rRNA gene and targeted metabolomics sequencing. The fecal microbiota transplantation (FMT) was used to investigate the role of gut microbiota in O. laneus treatment. O. laneus effectively reduced systemic inflammation, pancreatic damage, and intestinal barrier dysfunction in AP mice. We observed significant enrichment of pathogens along with depletion of second BAs (7-KDA) in AP mice, and these alterations were reversed by O. laneus. FMT experiment showed that the protective roles of O. laneus depended on gut microbiota. O. laneus ameliorated AP via activating intestinal FXR and inhibiting NLRP3 inflammasome in vivo. In vitro and vivo studies showed that 7-KDA protected AP. Taken together, O. laneus could mitigate AP-induced intestinal barrier dysfunction by reversing the disorderd gut microbiota, BAs metabolism, and modulating FXR/NLRP3 pathway.