Salvia miltiorrhiza-derived nanovesicles-microRNAs reshape the gut microbiota of ApoE -/- mice to improve atherosclerosis

The alterations in gut microbiome play an essential role in cardiovascular diseases. However, the relationship between the composition and function of gut microbiota and cardiovascular disease is not fully understood.This study explored the role of a high-fat diet and gut microbiota in the pathogenesis of atherosclerosis and the mechanism of Salvia miltiorrhiza-derived nanovesicles (SDNVs) intervention in atherosclerosis through regulating gut microbiota.The particle size of SDNVs is concentrated between 30-120nm, with a typical disc or hemispherical structure that conforms to the characteristics of extracellular vesicles. After oral administration of SDNVsDir, it is mainly distributed in the stomach and intestines of mice, and Novel-36 and Novel-12 miRNAs from SDNVs stably exist in the gut microbiota of AS mice. The gut microbiota of atherosclerosis model mice fed with a high-fat diet changed significantly, and the diversity of gut microbiota decreased. SDNVs reshape the species composition and function of gut microbiota in AS mice, increase the number of species in the microbiota and concentration of beneficial bacteria such as Bifidobacterium, increase the relative abundance of Bacteroidetes, Chlamydia, and Actinobacteria, reduce the relative abundance of Firmicutes, Novel-12 miRNA and Novel-36 mRNA target g_Eubacterium eubacterium, downregulate the expression of the CutC gene, affect liver FMO3 levels and activity, reduce TMA and TMAO production, improve blood lipids and inflammatory factors, and slow down the formation of aortic plaques in AS mice. Partial recovery of energy metabolism, amino acid metabolism, and nucleotide metabolism.SDNVs can improve atherosclerotic plaques and reduce blood lipids and inflammatory factors in serum through the SDNVs-miRNA/gut microbiota -TMA-TMAO pathway, thus playing an anti-atherosclerotic role.