Protective Effect of <i>Enterococcus faecium</i> Against Alcohol-Induced Acute Liver Injury Via Extracellular Vesicles in Rats

The beneficial effects of probiotics on alcohol-induced liver injury have been studied, but the mechanisms by which <i>Enterococcus</i> regulates liver function are still under investigation. In this study, we examined <i>Enterococcus faecium</i> (Efm) and <i>E. faecium</i>-derived extracellular vesicles (EfmEVs) to provide a protective effect against ethanol-induced liver injury in rats. We evaluated the impact of EfmEVs on liver histological lesions, antioxidative function, alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and serum ALT, AST, blood alcohol concentration. The results demonstrated that pretreatment with Efm significantly ameliorated ethanol-induced liver injury. Efm pretreatment mitigated the decline in ethanol-induced liver antioxidant indicators (malondialdehyde, superoxide dismutase, and glutathione peroxidase. Additionally, Efm pretreatment significantly reduced ethanol-induced ALT activities in the liver and serum, potentially by lowering blood ethanol concentration. Further, functional studies on three bioactive components (inactivated Efm, EfmEVs, and EVs-free supernatants) from the bacterial culture revealed that EVs were primarily responsible for the liver-protective effect. Moreover, EVs secretion contributed to the overall liver-protective effect of Efm. In summary, EfmEVs mediated the protective effect of Efm against ethanol-induced liver injury, potentially by improving antioxidative function and lowering blood ethanol concentration. These findings suggest that EfmEVs could serve as a potential antioxidative strategy to alleviate alcohol-induced acute liver injury.