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.