Targeted bile acids and gut microbiome profiles reveal the hepatoprotective effect of WZ tablet(Schisandra sphenanthera extract) against LCA-induced cholestasis

Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera(Wuzhi tablet, WZ) can significantly protect against lithocholic acid(LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration.However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCAinduced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.