Abstract: This study explored the ameliorative effect of daidzein (DAI) on alcoholic liver disease (ALD) in rats and examined the underlying mechanism using transcriptomics and high-throughput 16S rRNA sequencing. Hepatic injury, lipid and bile acid metabolism, and the expression of related proteins in the rat model of ALD were detected through biochemical analysis, pathological examination, and Western blotting. The findings indicated that DAI substantially alleviated alcohol-induced hepatic injury, oxidative stress, and inflammation, while decreasing the serum levels of total cholesterol and total bile acids, and decreasing lipid accumulation and cholestasis. Transcriptomic analysis revealed that DAI could reduce the synthesis of bile acid synthesis and promote its excretion through the bile secretion pathway, restoring the homeostasis of bile acid metabolism. In addition, DAI could also enhance the β-oxidation of fatty acids and ameliorate lipid metabolism disorders in the liver through the peroxisome proliferator-activated receptor (PPAR) signaling pathway. The results of 16S rRNA sequencing demonstrated that DAI intervention effectively alleviated alcohol-induced gut microbiota dysbiosis. Specifically, it reversed the dysregulated Firmicutes/Bacteroidetes ratio. At the genus level, DAI significantly modulated the relative abundance of Oscillospira, a key producer of butyrate. In conclusion, DAI can improve bile acid and lipid metabolism and regulate the gut​ microbiota, representing a promising functional component with great potential in the prevention and treatment of ALD.

Key words: daidzein; alcoholic liver disease; bile acid; lipid metabolism; gut microbiota