Role of the gut microbiota–bile acid axis in liver fibrosis based on microbiomics and targeted metabolomics

BACKGROUND: Effective diagnoses and treatments for liver fibrosis (LF) are lacking. The gut microbiota (GM) -bile acid (BA) axis is critically associated with LF development and may represent a potential target for delaying or reversing LF. METHODS: We combined fecal microbiomics and BA-targeted metabolomics to characterize the GM-BA axis in rats with carbon tetrachloride (CCl₄) -induced LF and used fecal microbiota transplantation (FMT) and probiotics (Bifidobacterium quadruple viable tablet solution) to regulate the GM-BA axis to investigate the role of the GM-BA axis in LF and its related mechanisms. RESULTS: The GM composition and GM β-diversity differed significantly between the control and model rats. Clostridia and others were significantly increased, whereas Bifidobacteriales and others were significantly decreased in model rats. Serum BA metabolism differed significantly between the groups. The concentrations of 19 BAs were significantly increased in model rats. FMT improved the disordered GM by increasing Bifidobacteriales and others and decreasing Clostridia and others. Probiotics improved the disordered GM by decreasing Clostridia, Lachnospiraceaᵢncertaeₛedis and others. FMT and probiotics improved BA metabolism by decreasing BAs such as tauroursodeoxycholic acid (TUDCA). FMT and probiotics were associated with a reduced degree of LF in model rats. CONCLUSIONS: The GM-BA axis is strongly associated with LF, and the use of FMT and probiotics may contribute to regulating the GM-BA axis and to alleviating LF.