Synergistic Inhibitory Effect of the Gut Microbiome and Lithocholic Acid on Liver Fibrosis

Abstract Background: Lithocholic acid are essential signaling molecules that mediate the relationship between the gut microbiome and liver function by regulating inflammation. The purpose of this study is to investigate the role of lithocholic acid in liver fibrosis. Methods: A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of lithocholic acid, and the effects of lithocholic acid were evaluated by serum biochemical analysis and liver histology. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively. Results: Lithocholic acid treatment increased the recruitment of NK cells and reduced the activation of NKT cells, and reduced M1 macrophages differentiation and increased M2 macrophages differentiation. Furthermore, the lithocholic acid prevented inflammatory liver disease by reducing TNF-α and IL-22 secretion. However, the effect of lithocholic acid disappeared when the host gut microbiome was treated with antibiotics. Conclusions: It showed that the activation of lithocholic acid-mediated signaling was linked to the inhibition of inflammation and improvement of liver fibrosis. The role of lithocholic acid in liver fibrosis is mediated by the gut microbiome. The association between the gut microbiome, lithocholic acid, and liver function can serve as a therapeutic target for liver fibrosis.