In　this　study,　we　investigated　the　ameliorative　effects　of　selenium-enriched　Lactobacillus　fermentum　FZU3103　(Lf@Se)　and　its　pathway　on　alcoholic　liver　injury　(ALI)　in　mice.　The　results　showed　that　Lf@Se　was　superior　to　Lf　and　inorganic　selenium　in　alleviating　ALI.　Oral　Lf@Se　effectively　prevented　lipid　metabolism　disorders,　improved　liver　function,　promoted　alcohol　metabolism,　and　alleviated　liver　oxidative　damage　in　mice.　16S　amplicons　sequencing　indicated　that　Lf@Se　intervention　modulated　intestinal　flora　homeostasis　by　increasing　(decreasing)　the　abundance　of　beneficial　bacteria　(harmful　bacteria),　which　is　associated　with　the　improvement　of　liver　function.　Besides,　Lf@Se　intervention　altered　the　liver　metabolic　profile,　and　the　characteristic　biomarkers　were　mainly　involved　in　tyrosine　metabolism,　retinol　metabolism,　galactose　metabolism,　and　primary　bile　acid　biosynthesis.　Additionally,　Lf@Se　intervention　regulated　liver　gene　expression　for　lipid　metabolism　and　oxidative　stress.　Western　blot　analysis　revealed　increased　expression　levels　of　intestinal　tight　junction　proteins　after　Lf@Se　intervention,　thereby　ameliorating　alcohol-induced　intestinal　barrier　damage.　©　2024　American　Chemical　Society.