Isolation of Lactobacillus plantarum HFY05 from Naturally Fermented Yak Yoghurt and Its Protective Effects against Alcoholic Liver Injury in Mice

Lactobacillus plantarum HFY05 (LP-HFY05), a novel strain isolated and identified from traditional yak Yoghurt in Hongyuan, Sichuan Province of the Qinghai-Tibet Plateau, was investigated for its probiotic potential and hepatoprotective effects against alcoholic liver injury. In vitro assessments revealed that LP-HFY05 possessed superior tolerance to artificial gastric acid and bile salts compared to the commercial strain Lactobacillus delbrueckii subsp. bulgaricus (LDSB). In a murine model of chronic alcohol-induced liver injury, intervention with LP-HFY05 significantly ameliorated hepatic pathology and reduced the liver index. It systematically improved serum biochemical profiles by downregulating the levels of liver injury markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), lipids (triglyceride, total cholesterol), uremic toxin (blood urea nitrogen), and oxidative metabolite (malondialdehyde, MDA), while upregulating albumin and key antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase). Furthermore, LP-HFY05 treatment suppressed systemic inflammation, evidenced by decreased serum concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-12, tumour necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). Mechanistic studies utilising quantitative PCR and Western blot analysis demonstrated that LP-HFY05 modulated the hepatic NF-κB pathway and redox system. It upregulated the expression of antioxidant enzymes (manganese-SOD, copper-zinc-SOD, and CAT) and endothelial/neuronal nitric oxide synthases (eNOS/nNOS), while downregulating inducible NOS (iNOS) and nuclear factor-κB-p65 (NF-κB p65) expression. Concurrently, LP-HFY05 restored gut microbial homeostasis, increasing the abundance of beneficial genera (Bacteroides, Bifidobacterium, Lactobacillus) and reducing harmful bacterial populations (Firmicutes, Actinobacteria, Proteobacteria, Enterobacteriaceae) in the faeces of injured mice. The hepatoprotective efficacy of LP-HFY05 was superior to that of LDSB and comparable to the positive control drug silymarin. In conclusion, Lactobacillus plantarum HFY05, a robust probiotic candidate from traditional fermented dairy, demonstrates significant protective effects against alcoholic liver injury. Its multi-faceted actions involve alleviating oxidative stress, inhibiting inflammation, regulating the NF-κB and NOS pathways, and restoring intestinal microbiota balance, positioning it as a high-quality microbial resource for potential therapeutic or functional food applications.