Abstract:Intrahepatic cholestasis is a pathological condition caused by abnormal bile secretion and excretion, which has a adverse impact on human health. A typical model of intrahepatic cholestasis induced by α-naphthylisothiocyanate (ANIT) was constructed to investigate the alleviating effect of Bifidobacterium longum CCFM1077 on intrahepatic cholestasis in mice. The results showed that B. longum CCFM1077 could ameliorate liver histological damage induced by ANIT, reducing the levels of major liver function-related enzymes in serum such as aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), as well as the levels of bile acids (BAs). Furthermore, B. longum CCFM1077 could significantly upregulate the expression of fxr gene by activating the enterohepatic axis FXR-FGF-15 signaling, thereby inhibiting the expression of cyp7a1, a gene involved in the synthesis of BAs. This strain significantly increased the abundance of gut commensals, such as Lactobacillus and Bifidobacterium, with high bile salt hydrolase activity, decreased the levels of bound BAs (T-β-MCA, TCDCA, and TUDCA) in the liver of mice, and increased the levels of free BAs (CDCA, CA, DCA, and UDCA), thus promoting BAs excretion. B. longum CCFM1077 also reduced the relative abundance of Escherichia_Shigella and upregulated the relative abundance of Ruminococcaceae_UCG_014 in the intestine of mice. These results indicate that intervention with B. longum CCFM1077 can inhibit the anabolism of BAs to alleviate intrahepatic cholestasis, which may be related to the regulation of the strain on the gut microbiota structure of mice.
