Gut Microbiota and Liver Metabolism Regulation Mediate the Protective Effects of Inactivated Selenium-Enriched Yeast Against Alcohol-Induced Liver Damage in Mice

Inactivated Selenium-enriched yeast (YSe), as an organic source of selenium with multiple physiological activities, has attracted widespread attention. However, its potential to alleviate alcoholic liver injury (ALD) and its underlying mechanisms remain largely unexplored. This study explores the protective effects of inactivated YSe intervention on ALD in mice and clarifies its mechanism of action. The results indicated that, at the same selenium dose, inactivated YSe intervention was superior to inorganic selenium (sodium selenite) in alleviating ALD. Specifically, high-dose inactivated YSe significantly reduced the levels of serum ALT and AST in alcohol-exposed mice (38.69% and 24.67%, respectively), increased the level of HDL-C (16.83%), and effectively improved alcohol-induced lipid metabolism disorders and liver oxidative damage. At the same time, it significantly increased the concentration of short-chain fatty acids (SCFAs) in feces. 16S rRNA sequencing indicates that inactivated YSe intervention enhances the abundance of beneficial flora (such as <i>Blautia</i>, <i>Oscillibacter</i>, <i>Anaerotruncus</i>, <i>Butyricicoccus</i>, and <i>Ruminiclostridium</i>) and simultaneously inhibits potentially harmful microbiota (such as <i>xylanophium</i>, <i>Escherichia-Shigella</i> and <i>oscilliumspirates</i>) to restore the homeostasis of the intestinal microbiota in ALD mice. Liver metabolomics analysis revealed that inactivated YSe intervention significantly altered the liver metabolic profile. The core pathways that are regulated by YSe after alcohol disruption include glutathione metabolism, purine metabolism, riboflavin metabolism, etc. In conclusion, this study demonstrates that inactivated YSe can effectively alleviate ALD in mice by regulating the structure of the intestinal flora and restoring liver metabolic homeostasis, providing a scientific basis for its potential functional food component in the prevention and auxiliary management of ALD.