BuYangHuanWu decoction alleviates atherosclerosis by regulating intestinal microbiota and metabolites in ApoE-/- mice fed with HFD

Abstract

Background Traditional Chinese herbal prescription BuYangHuanWu decoction (BHD) works well in treating atherosclerosis. However, the mechanism of BHD in atherosclerosis has not been fully elucidated. We aimed to determine whether BHD could alleviate atherosclerosis by altering the microbiome-associated metabolic changes in atherosclerotic mice. Methods An atherosclerotic model was induced in ApoE−/− mice fed a high-fat diet (HFD), and BHD were administered by gavage for 12 weeks at 8.4g/kg/d and 16.8g/kg/d. Atherosclerotic plaque size, composition, serum lipid profile, as well as inflammatory cytokines were assessed. Mechanistically, metabolomic and micro biota profiling were analyzed using liquid chromatography mass spectrometry (LC-MS) and 16S rRNA gene sequencing, respectively. Further, intestinal microbiota and atherosclerosis-related metabolic parameters were correlated using Spearman analysis. Results Atherosclerotic mice treated with BHD showed a reduction in plaque area, aortic lumen occlusion, and lipid accumulation in the aortic root. 9 perturbed serum metabolites were significantly restored along with the relative abundance of micro biota at the family and genus levels, but not at the phylum level. Gut microbiota improvements were strongly negatively correlated with improved metabolite levels. Conclusions BHD treatment effectively slows the progression of atherosclerosis by regulating altered intestinal microbiota and perturbed metabolites. Detailed analysis of these interactions between intestinal microbes and metabolites affected by BHD will help in the development of new anti-atherosclerosis medications.