Peanut skin extract ameliorates high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and gut microbiota in ApoE−/− mice

Atherosclerosis (AS) is a serious threat to the health and life of humans worldwide. The mitigating effect of polyphenol compounds from peanut skin extract (PSE) on AS has attracted great research attention. However, the mechanism underlying this mitigating effect remains poorly understood. This study aims to investigate the preventive effect of PSE on high-fat diet-induced AS in mice and explore the underlying mechanisms. PSE treatment significantly reduced atherosclerotic plaques, particularly at high doses. Dietary PSE intervention obviously alleviated the lipid metabolism disorder in ApoE-/- mice by reducing the serum TC and LDL-C contents and increasing the HDL-C content. In addition, PSE intervention significantly decreased the level of pro-inflammatory cytokines TNF-α and IL-6 and increased that of anti-inflammatory IL-10, thus exhibiting a significant anti-inflammatory effect. More interestingly, analysis of the 16S rRNA gene sequence revealed that PSE could significantly alter the community composition of the gut microbiota. Specifically, PSE enhanced the abundance of Roseburia, Rothia, Parabacteroides and Akkermansia, and reduced that of Bilophila and Alistipes. Some of these intestinal bacteria exhibited good anti-inflammatory effects, which are related to the production of short chain fatty acids. Thus, the anti-atherosclerotic effect of PSE may be partly attributed to changes in the composition and function of gut microbiota, which may be closely associated with its anti-inflammatory effect. Moreover, untargeted metabolomics analysis indicated that PSE could regulate the levels of differential metabolites in the liver, serum and fecal samples.