Abstract:i>Lactiplantibacillus plantarum is a probiotic with multiple health benefits. To investigate its effects against alcoholic liver injury, 16 strains of Lactiplantibacillus plantarum were isolated from traditional fermented foods. Their ethanol degradation capacity and effects on alcohol dehydrogenase and acetaldehyde dehydrogenase activities were evaluated, and 8 strains that demonstrated high alcohol metabolism rates and reduced hepatic oxidative stress levels were preliminarily screened. Subsequent assessment of antioxidant capacity, acid resistance, and bile salt tolerance of these 8 strains was carried out, and an optimal strain, Lactiplantibacillus plantarum FS5-5 was identified. An alcoholic liver injury mouse model was established to investigate the effects of Lactiplantibacillus plantarum 5-5. Results showed that FS5-5 exhibited a strong alcohol metabolism capability with alcohol dehydrogenase and acetaldehyde dehydrogenase activities reaching 35.99U/mL and 162.11U/mL, respectively. Meanwhile, high-dose FS5-5 significantly prolonged drunkenness duration, shortened sobering time, and reduced serum ethanol concentration (P<0.05). Furthermore, the high-dose FS5-5 group (1×109CFU/mL) notably alleviated pathological liver damage, decreased hepatic malondialdehyde and triglyceride levels, increased glutathione content, reduced serum transaminases and inflammatory factor levels, enhanced antioxidant enzyme activity, effectively mitigated hepatic oxidative stress (superoxide dismutase level) and inflammatory injury (IL-6, IL-1β, TNF-α levels), and lowered total cholesterol content. Mechanistic studies demonstrated that this strain exerted hepatoprotective effects against alcoholic liver injury by regulating hepatic gene Nrf2, Cyp2e1, NF-κB, and Tlr4 expression, reducing pro-inflammatory cytokine levels, and alleviating oxidative stress and lipid accumulation. This research provided theoretical basis for developing functional foods with auxiliary protective effects against alcoholic liver injury.