Lactiplantibacillus plantarum BD7807 ameliorates high-fat diet-induced lipid metabolic disorders and intestinal...

Excessive dietary fat intake induces intestinal barrier dysfunction, and this may further lead to metabolic diseases and inflammatory bowel disease (IBD). Probiotic intervention strategies are effective in alleviating diet-induced intestinal barrier dysfunction. This study revealed the alleviating effect of the probiotic Lactiplantibacillus plantarum BD7807 on lipid metabolism and intestinal barrier disorders caused by a high-fat diet (HFD). The results showed that strain BD7807 possessed excellent gut adaptability, lipid-lowering as well as antioxidant properties, and alleviated palmitic acid-induced barrier damage in Caco2 cells in vitro. Strain BD7807 reduced liver lipid accumulation in HFD mice and intestinal injury in vivo. Specifically, strain BD7807 up-regulated the expression of MUC2 protein, antimicrobial peptides and tight junction genes. Moreover, the proportion of regulatory T cells (Tregs) remarkedly increased after strain BD7807 treatment, thereby attenuating inflammatory response. Strain BD7807 also elevated the abundance of gut-beneficial bacteria, contributing to reduced intestinal inflammation and serum lipid levels. Mechanistically, strain BD7807 elevated intestinal short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate, which activated G protein-coupled receptor 43 (GPR43) while inhibiting histone deacetylase 3 (HDAC3) to restore intestinal barrier integrity. Concurrently, SCFAs-mediated activation of the hepatic GPR43-AMPK pathway suppressed the expression of liver lipid synthesis genes (Srebp2, Fasn, Srebp-1c, Cd36, and Acc), thereby reducing hepatic lipid accumulation. Further validation using the GPR43 inhibitor GLPG0974 confirmed that the protective effects of strain BD7807 on lipid metabolism and intestinal barrier function were partially dependent on the SCFAs-GPR43 signaling axis. Overall, L. plantarum BD7807 has the potential to ameliorate HFD-induced metabolic disorders.