Lactobacillus plantarum P9 ameliorates dysfunctional immune and metabolic homeostasis along the gut–liver axis in a nonalcoholic fatty liver disease with low-grade colitis mouse model

Disrupting the balance between intestinal microbiota and mucosal immune responses impair gut barrier function and upregulates the inflammatory response, leading to the development of nonalcoholic fatty liver disease (NAFLD). The probiotic Lactobacillus plantarum P9 has strong immunoregulatory effects and ameliorates NAFLD. In an NAFLD mouse model, L. plantarum P9 modulated metabolic homeostasis by decreasing levels of plasma triglyceride and low-density lipoprotein and suppressing the secretion of proinflammatory mediators in the plasma. L. plantarum P9 maintained gut barrier function and microbiota structure by inducing the tight junction protein expressions and decreasing plasma D-mannitol level, as well as restoring the abundance of Desulfovibrio and Colidextribacter and lowering the abundance of Faecalibaculum and Erysipelatoclostridium, which are NAFLD-specific gut microbiota. L. plantarum P9 could maintain lipid homeostasis in hepatocytes. RNA-Seq and western blot analyses revealed that L. plantarum P9 activated the autophagy–lipophagy pathway through p62, LC3-II/LC3-I, and peroxisome proliferator-activated receptor (PPAR)-α. This study provides insights into the protective effect of L. plantarum P9 in gut barrier integrity to maintain liver function along the gut–liver axis.