Western Diet Aggravated Carbon Tetrachloride‐Induced Chronic Liver Injury by Disturbing Gut Microbiota and Bile Acid Metabolism

Scope The high‐fat, high‐sucrose, and low‐fiber Western diet (WD) is popular in many countries and affects the onset and progression of many diseases. This study is aimed to explore the influence of the WD on chronic liver disease (CLD) and its possible mechanism. Methods and results C57BL/6 mice are given a control diet (CD) or WD and CLD is induced by intraperitoneally injecting carbon tetrachloride (CCL4) twice a week for 8 weeks. The WD aggravated CCL4‐induced chronic liver injury, as evidenced by increased serum transaminase levels, worsened hepatic inflammatory response, and fibrosis. Gut microbiota is disturbed in mice treated with CCL4+WD (WC group), manifested as the accumulation of Fusobacteria, Streptococcaceae, Streptococcus, Fusobacterium, and Prevotella and the depletion of Firmicutes, Lachnospiraceae, and Roseburia. Additionally, increased hepatic taurocholic acid in the WC group activated sphingosine‐1‐phosphate receptor 2, which is positively correlated with hepatic fibrosis and inflammation parameters. Mice in the WC group have higher fecal primary bile acid (BA) levels and lower fecal secondary/primary BA ratios. Serum FGF15 levels are also elevated in the WC group, which is positively correlated with hepatic inflammation. Conclusion WD accelerates the progression of CLD which is associated with changes in the gut microbiota and BA metabolism. Western diet (WD) promotes carbon‐tetrachloride‐induced chronic liver disease (CLD). On the one hand, WD disturbs gut microbiota with the depletion of Lachnospiraceae and accumulation of Streptococcaceae. On the other hand, WD changes hepatic and fecal bile acid metabolism which contributes to the exacerbation of carbon‐tetrachloride‐induced CLD by suppressing SHP, activating S1pr2, and increasing the secretion of FGF15.