Lactobacillus plantarum ameliorates high-fat-diet-induced dyslipidemia via cholesterol metabolism and gut microbiota modulation.

Dyslipidemia, a typical metabolic disorder, is predominantly characterized by elevated levels of total cholesterol (TC) and/or triglycerides (TG), with disruption of cholesterol homeostasis serving as a significant contributing factor. This study demonstrated that Lactobacillus plantarum DY6 alleviated high-fat diet-induced dyslipidemia in mice by improving lipid profiles and reducing hepatic injury. Mechanistically, L. plantarum DY6 reduced the endogenous cholesterol synthesis by downregulating hepatic sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) expression. It also inhibited intestinal cholesterol absorption via suppressing Niemann-Pick C1-Like 1 (NPC1L1) expression and activated the hepatic liver X receptor alpha (LXRα) signaling pathway, which upregulated the expression of ATP-binding cassette transporters ABCG5 and ABCG8 in the small intestine to enhance cholesterol efflux. Furthermore, L. plantarum DY6 modulated the composition of the gut microbiota, facilitated the proliferation of beneficial bacteria, increased the production of short-chain fatty acids (SCFAs), and regulated hepatic metabolite profiles, collectively contributing to the improvement of dyslipidemia. In conclusion, L. plantarum DY6 exerted multi-target regulatory effects via the gut-liver axis, offering a promising therapeutic strategy for preventing and mitigating high-fat diet-induced dyslipidemia.