Gut Microbiota Composition Affects Procyanidin A2-Attenuated Atherosclerosis in ApoE-/- Mice by Modulating the Bioavailability of Its Microbial Metabolites

Procyanidin A2 (PCA2) has been shown to improve lipid metabolism. However, it remains to know whether it can play a role in preventing atherosclerosis (AS) through gut microbiota. This study examined the effect of PCA2 on high fat diet (HFD)-induced AS in ApoE(-/-) mice with an intact and antibiotic-depleted microbiota. PCA2 administration for 12 weeks attenuated HFD-induced AS in ApoE(-/-) mice, evidenced by obviously alleviating the histological abnormalities of the aorta, lipid accumulation, oxidative stress, and inflammation, which were accompanied by downregulating the expression of vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 and upregulating peroxisome proliferator-activated receptor gamma, cholesterol 7 alpha-hydroxylase, and ATP-binding cassette transporter A1. Moreover, PCA2 treatment reshaped the gut microbiota imbalance caused by HFD, especially reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Verrucomicrobia. However, antibiotic intervention almost offset the alleviation of AS by PCA2 and prevented the biotransformation of PCA2 by gut microbiota, thus resulting in a 2327.21-6.27-fold decrease in its microbial metabolites of plasma. There was a marked correlation among the microbiota composition, the bioavailability of PCA2-derived microbial metabolites, and AS indicators. The findings indicate that the gut microbiota robustly influences the bioavailability of microbial metabolites that may partially drive the AS resilience property of PCA2.

Automated summary

PCA2 administration was found to attenuate HFD-induced AS in ApoE(-/-) mice by improving gut microbiota imbalance and regulating pathological abnormalities, lipid accumulation, oxidative stress, and inflammation. However, antibiotic intervention offset the benefits of PCA2 and prevented gut microbiota-mediated biotransformation, resulting in a significant decrease in microbial metabolites. The study highlights the significant influence of gut microbiota on the bioavailability of microbial metabolites and the potential of PCA2 in preventing AS.