Interplay between diet, the gut microbiome, and atherosclerosis: Role of dysbiosis and microbial metabolites on inflammation and disordered lipid metabolism

Atherosclerosis remains the leading cause of death worldwide. Lifestyle modification, including diet and exercise, is recommended to be the primary prevention strategy for atherosclerosis. Dietary patterns have been shown to be strongly associated with atherosclerosis risk. In addition, diet-induced modulation of gut microbiota and the resultant microbial metabolites may influence the progression of atherosclerosis. This review summarizes the role of gut dysbiosis and different microbial metabolites in atherosclerosis, and how different diets may promote or prevent atherosclerosis through gut microbiome modulation. Non-digestible carbohydrates can increase the production of microbial metabolite short-chain fatty acids in the gut, protecting the gut barrier and decreasing overall systemic inflammation. High animal protein/L-carnitine diets may contribute to gut microbiome-dependent production of trimethylamine N-oxide, contributing to atherosclerosis by increased foam cell formation, decreased reverse cholesterol transport (RCT), and pro-thrombotic actions. Western/high-fat diets can increase the gut microbiome production of secondary bile acids and influence downstream signaling via farnesoid X receptor and lead to dysbiosis. Dysbiosis leads to the translocation of lipopolysaccharide (LPS) to the bloodstream by compromising the gut barrier. LPS can activate Toll-like receptor 4 signaling and decrease RCT to exacerbate atherosclerosis. Studies showing a relationship between the gut microbiome and atherosclerosis are still mostly through correlation, while causal pathways are still being uncovered. Future research should integrate proteomics and metabolomics to 16S microbiome sequencing to get a complete picture of the pathways, metabolites, and microbes involved, and to elucidate the complex interaction between the gut microbiome and atherosclerosis.