(P03-015-23) Effect of Protocatechuic Acid on Gut Microbiota and Atherosclerosis

Objectives: Atherosclerosis severely threatens human health mainly via the plaque accumulation inside aorta. Trimethylamine N-oxide (TMAO) is a gut microbial metabolite of dietary choline, betaine, carnitine and phosphatidylethanolamine. TMAO can induce the atherosclerosis. Protocatechuic acid (PCA) is a type of natural phenolic acid, which exists in various plants. The objective of this study is to investigate the effect of PCA on gut microbiota and TMAO-induced atherosclerosis.

Methods: ApoE^-/- mice was used as an animal model of atherosclerosis. In brief, 45 ApoE^-/- mice were divided into five groups given one of the five diets, namely a low-fat diet (LFD), a western diet (WD), a WD+TMAO diet, a WD+TMAO+low-PCA diet, and a WD+TMAO+high-PCA diet. The feeding experiment lasted 12 weeks. Aortic atherosclerotic plaque, plasma, hepatic and fecal fatty acids and gut microbiota were measured. In addition, the expression of genes involved in fatty acid metabolism were quantified at both transcriptional and translational levels.

Results: PCA didn’t influence TMAO absorption, but it exerted an anti-atherosclerotic ability with reduced plaque area in thoracic aorta. Body weight gain, the weight of adipose tissues also decreased after PCA supplementation for 12 weeks. PCA was found to decrease the plasma levels of proinflammatory cytokines. Besides, PCA could promote the elimination of fatty acids because mice fed with PCA had lower hepatic and higher fecal fatty acids, respectively. PCA also altered the relative genus abundance of Rikenella, Turicibacter, Clostridium_sensu_stricto, Bifidobacterium, Enterorhabdus and Lactococcus.

Conclusions: PCA attenuated TMAO-exacerbated atherosclerosis by mitigating inflammation, regulating lipid metabolism and altering gut microbiota in ApoE^-/- mice. The research results will lay a scientific foundation using PCA as a dietary cardio-protective supplement.

Funding Sources: This work was supported by the General Research Fund of Hong Kong.