Effect of Tetrastigma hemsleyanum leaves and Extract supplementation on liver metabolomics and the gut microbiota in alcohol-induced liver injury

Alcoholic liver disease (ALD) is caused by chronic heavy alcohol consumption and is characterized by lipid metabolism disorders, oxidative stress, and hypersecretion of proinflammatory cytokines. Tetrastigma hemsleyanum leaves (THL), a popular functional food in China, have good anti-inflammatory, antioxidant, and liver protection effects. However, whether THL extracts improve alcoholic liver disease and the underlying mechanism of action have not been determined. Therefore, in this study, we used a C57BL/6J male mouse model to investigate the effect of THL extract on ALD and to explore the underlying mechanism involved preliminarily. The alleviation of alcohol-induced liver dysfunction and changes in lipid metabolism-related pathways were observed after THL extract administration stimulated fatty acid synthesis and fatty acid β-oxidation by modulating the expression levels of related mRNAs and genes, thereby alleviating lipid accumulation and oxidative stress in the liver. The composition and abundance of the gut microbiota in mice also underwent alterations. Collectively, these findings suggest that supplementation with THL extract can mitigate liver damage and reduce hepatic lipid accumulation in mice with alcoholic fatty liver disease. It regulates hepatic metabolism and generates various metabolites associated with diminished lipid buildup, such as Plafibride, LysoPI (20:4(5Z,8Z,11Z,14Z)/0:0), 1,3,7-trimethyluric acid, and phytol. Moreover, it impacts specific gut microbiota in mice with alcoholic fatty liver disease including Bacteroides and other beneficial microorganisms while enhancing the production of short-chain fatty acids to improve the intestinal microenvironment.