The interplay between microbial metabolites and macrophages in cardiovascular diseases: A comprehensive review.

• Microbial metabolites can modulate macrophage activation and polarization, leading to the development and progression of cardiovascular diseases. • Short-chain fatty acids produced by the gut microbiome can promote anti-inflammatory macrophage phenotypes and reduce atherosclerosis development. • Trimethylamine N-oxide (TMAO) produced by the gut microbiome can promote pro-inflammatory macrophage phenotypes and contribute to atherosclerosis development. • Microbial metabolites can modulate the expression of genes involved in macrophage function, such as cholesterol metabolism and inflammation. • Targeting microbial metabolites through dietary interventions, probiotics, or pharmacological approaches may be a potential therapeutic strategy for treating and preventing cardiovascular diseases. The gut microbiome has emerged as a crucial player in developing and progressing cardiovascular diseases (CVDs). Recent studies have highlighted the role of microbial metabolites in modulating immune cell function and their impact on CVD. Macrophages, which have a significant function in the pathogenesis of CVD, are very vulnerable to the effects of microbial metabolites. Microbial metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), have been linked to atherosclerosis and the regulation of immune functions. Butyrate has been demonstrated to reduce monocyte migration and inhibit monocyte attachment to injured endothelial cells, potentially contributing to the attenuation of the inflammatory response and the progression of atherosclerosis. On the other hand, TMAO, another compound generated by gut bacteria, has been linked to atherosclerosis due to its impact on lipid metabolism and the accumulation of cholesterol in macrophages. Indole-3-propionic acid, a tryptophan metabolite produced solely by microbes, has been found to promote the development of atherosclerosis by stimulating macrophage reverse cholesterol transport (RCT) and raising the expression of ABCA1. This review comprehensively discusses how various microbiota-produced metabolites affect macrophage polarization, inflammation, and foam cell formation in CVD. We also highlight the mechanisms underlying these effects and the potential therapeutic applications of targeting microbial metabolites in treating CVD. [ABSTRACT FROM AUTHOR]