Compound probiotics mitigate alcohol-induced liver injury in mice by regulating the gut microbiota and TLR4/NF-κB pathway

Abstract Alcohol-related liver disease (ALD) is a worldwide disorder with limited treatment options. As a result, probiotics are emerging as a potential complementary therapy. This research investigated the efficacy of the compound probiotics (Bifidobacterium animalis subsp. lactis GOLDGUT-BB18 and Lactobacillus acidophilus GOLDGUT-LA100: BB18+LA100) on alleviating alcohol-induced liver damage in mice. The results indicated BB18+LA100 supplementation mitigated liver injury by normalizing transaminase levels, ameliorating lipid profiles, and reducing hepatic steatosis diminishing steatosis of liver. Simultaneously, BB18+LA100 supplementation inhibited pro-inflammatory cytokines while elevating IL-10 levels, and established redox homeostasis by elevating antioxidant defenses and diminishing lipid peroxidation. Transcriptome analyses revealed that BB18+LA100 attenuated alcohol-induced dysregulation, particularly by supressing the TLR4/NF-κB pathway, with efficacy comparable to silymarin. Importantly, RT-qPCR and western blot results further confirmed these transcriptomic finding, validating the inhibitory effect of BB18+LA100 on inflammatory gene and protein expression. Moreover, BB18+LA100 supplementation increased gut microbiota diversity and the abundance of beneficial taxa, modulated amino acid and carbon metabolism, and enhanced the synthesis of short-chain fatty acids (SCFAs). Collectively, BB18+LA100 exerts robust hepatoprotective effects against alcohol-induced liver injury by maintaining gut-liver axis homeostasis and coordinating microbiota-driven metabolic and inflammatory regulation, highlighting its potential as a probiotic-based strategy for the prevention and management of ALD.