Prevotella copri ameliorates cholestasis and liver fibrosis in primary sclerosing cholangitis by enhancing the FXR signalling pathway

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by bile duct inflammation, fibrosis, bile acid (BA) metabolism disorders and gut microbiota dysbiosis. At present, the aetiology and pathogenesis of PSC are not clear, and there is no specific or effective treatment available. Therefore, new research perspectives are needed to explore effective methods to treat PSC and improve symptoms. The intestinal microbiota of patients with PSC is known to be significantly different from that of healthy people. By comparing differentially abundant bacterial genera in PSC patients, it was found that the abundance of Prevotella copri (P. copri) was significantly decreased, suggesting that this species may have a protective effect against PSC disease. Therefore, comprehensively exploring the role and possible function of P. copri in the disease process is worthwhile. In this study, a PSC mouse model was established by feeding mice a customized diet supplemented with 0.1% (w/w) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for one week, and the abundance of P. copri was confirmed to be decreased in this model. Previous studies in patients and animal models have demonstrated that gut microbiota intervention is an acceptable treatment for some diseases. We found that intervention with P. copri could significantly improve cholestasis and liver fibrosis by enhancing the FXR-related signalling pathway in PSC mice. Together, through the overall effect of P. copri on intestinal microbiota structure and its association with BAs, we speculate that P. copri intervention might be as potential biological treatment of PSC.