Ameliorative effects of chlorogenic acid on alcoholic liver injury in mice via gut microbiota informatics

Chlorogenic acid (CGA) is a functional phenolic acid widely used in food and medicine-related fields. It has been proved to be effective in the treatment of alcoholic liver disease (ALD). However, the exact mechanism by which CGA prevents ALD, especially from the crosstalk between gut and liver, has not been previously reported. This work was aimed to explore the protective effects of CGA against ALD and its relationships to gut-liver axis abnormalities. Experimental results showed the increased (p < 0.05) serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), low density lipoprotein (LDL), total cholesterol (TC) and triglyceride (TG) levels of mice fed with ethanol were ameliorated by supplementing with CGA. Moreover, CGA promoted the production of n-butyric acid by nearly 3 times (1.78 vs 0.62 nM, p < 0.01), a short-chain fatty acid that helps maintain the integrity of the intestinal barrier. Furthermore, CGA alleviated microbial dysbiosis, evidenced by the increased relative abundances of beneficial bacteria Muribaculaceae, Bacteroides, Alloprevotella, and Parabacteroides, and decreased that of opportunistic pathogens Eubacterium_nodatum, Eubacterium_ruminantium, and Anaerotruncus. Correlation analysis further elucidated the microbiota altered after CGA intervention was positively correlated with short-chain fatty acids and antioxidant indexes, while negatively correlated with inflammatory cytokines. In summary, these findings suggested the hepatoprotective effect of CGA was ascribed to the modulation of gut-liver axis homeostasis.