Heat-Inactivated Lactiplantibacillus plantarum H6 Potentiates Low-Dose Simvastatin Efficacy Against Hypercholesterolemia in Mice Through Gut Microbiota Modulation.

Due to the limited lipid-lowering effect of statins, combined lipid-lowering strategies have attracted much attention. This study aims to explore the improvement effect of the combined intake of postbiotics and low-dose simvastatin on hypercholesterolemic mice. In this study, mice with hypercholesterolemia model were established and administrated with low-dose simvastatin + inactivated Lactiplantibacillus plantarum H6 / surface layer protein / cell-bound exopolysaccharides for 8 weeks, it was found that the combined intake of iH6 and low-dose simvastatin could improve the blood lipid level of hypercholesterolemia mice, and the intake of iH6 did not affect the efficacy of simvastatin. The combined intake of iH6 and low-dose simvastatin significantly reduced the total TC levels in the serum, liver, ileum and feces of mice, as well as the serum LDL-C level compared with simvastatin alone. Moreover, it effectively improved liver injury, decreased the levels of serum ALT, AST and TBA, and alleviated liver oxidative stress, thereby protecting the liver. Further analysis of the intestinal microbiota and metabolites revealed that iH6 combined with low-dose simvastatin significantly increased the relative abundance of Alistipes, Enterorhabdus, Lachnospiraceae_NK4A136_group, norank_o__Clostridia_UCG-014 and Prevotellaceae_UCG-001 in the mouse gut, regulated the composition of the intestinal BA pool, especially secondary BAs, and maintained the dynamic balance of cholesterol levels in the body. In addition, compared with simvastatin alone, the combined effect of iH6 and low-dose simvastatin could increase the expression of transcriptional genes such as Ugt2b38, Cyp2e1, Cyp1a1, Cyp2c29, and Scd1 in the ileum, enhance the cholesterol metabolism-related pathways, and alleviate hypercholesterolemia in mice. In conclusion, this study evaluated the relationship between postbiotics (inactivated strains) and drug combination, aiming to reduce the use of drugs and promote the possibility of postbiotics as a drug companion, laying a foundation for the development and application of postbiotics in medical fields.