Comprehensive Analysis Of Bile Acid Profile And Interaction With Gut Microbiota In Primary Biliary Cholangitis

AIMS: Primary biliary cholangitis(PBC)is an immune-mediated progressive cholestatic liver disease,characterized by destruction of intrahepatic bile ducts.Accumulation of bile acids(BAs)contributes significantly to the pathogenesis of PBC.Here,we aimed to systematically investigate the composition of serum and fecal BAs in PBC,the interaction between BAs and gut microbiota,as well as the impact of UDCA treatment on BA and gut microbiota compositions.METHODS: Using a cross-sectional study,we analyzed BAs in a total of223 serum samples and 212 fecal samples from UDCA treatment-naive PBC and healthy controls,using UPLC-MS.Fecal DNA were analyzed by 16 s ribosomal DNA gene sequencing.Thence in a nested prospective study,a subset of patients was enrolled for BA and microbiota analysis before and after UDCA therapy.Matched healthy controls were included throughout.RESULTS: Serum and fecal BA profiles were altered in treatment-naive PBC.PBC with advanced disease stage or with inadequate response to UDCA,had even more pronounced changes in the composition of serum BA,but not in fecal,than patients with early disease stage or with biochemical response to UDCA.Increased conjugated/unconjugated BA ratio and decreased secondary/primary BA ratio in serum were associated with UDCA treatment-na(?)ve PBC.Furthermore,the proportions of serum and fecal secondary BAs were strongly correlated with PBC-associated genera.UDCA treatment led to decreased levels of taurine-conjugated BAs,which were associated with increased abundance of taurine-metabolizing bacteria Bilophila spp..CONLUSION: Our data reflect specific alterations of BA profiles and gut microbiota in PBC,reflecting the influences of microbial BA metabolism on deconjugation and dehydroxylation,and highlighting the potential for disease modulation by altering gut microbiota.