Microbiota-Mediated Immune Regulation in Atherosclerosis

Abstract

There is a high level of interest in identifying metabolites of endogenously produced or dietary compounds generated by the gastrointestinal (GI) tract microbiota, and determining the functions of these metabolites in health and disease. There is a wealth of compelling evidence that the microbiota is linked with many complex chronic inflammatory diseases, including atherosclerosis. Macrophages are key target immune cells in atherosclerosis. A hallmark of atherosclerosis is the accumulation of pro-inflammatory macrophages in coronary arteries that respond to pro-atherogenic stimuli and failure of digesting lipids that contribute to foam cell formation in atherosclerotic plaques. This review illustrates the role of tryptophan-derived microbiota metabolites as an aryl hydrocarbon receptor (AhR) ligand that has immunomodulatory properties. Also, microbiota-dependent trimethylamine-N-oxide (TMAO) metabolite production is associated with a deleterious effect that promotes atherosclerosis, and metabolite indoxyl sulfate has been shown to exacerbate atherosclerosis. Our objective in this review is to discuss the role of microbiota-derived metabolites in atherosclerosis, specifically the consequences of microbiota-induced effects of innate immunity in response to atherogenic stimuli, and how specific beneficial/detrimental metabolites impact the development of atherosclerosis by regulating chronic endotoxemic and lipotoxic inflammation.

Pathophysiology of Atherosclerosis

“…On the other hand, several metabolites produced by the gut microbiota can modulate systemic inflammation and contribute or prevent atherosclerosis development. The most studied one is trimethylamine-N-oxide (TMAO) [ 355 ], the oxidized form of trimethylamine (TMA). TMA is synthesized by gut microbiota after metabolizing diet choline and carnitine.…”

Nephroprotective activity ofVetiveria zizanioides(L.) Nash supplement in doxorubicin‐induced nephrotoxicity model of Wistar rats

“…In fact, the dietary supplement of V. zizanioides might be beneficial in enhancing the quality of life of kidney patients by preserving kidney functions and preventing/delaying the progression to an end‐stage kidney disease (Ash et al., 2014; Cosola et al., 2018). However, the possible role of gut microbiota in the pathogenesis of the kidney disease has been reported (Eshghjoo et al., 2021). Even though, diet is considered a major factor driving the composition and metabolism of the gut microbiota, the effect of dietary supplements on gut microbiota and its mechanistic links to bioactivities are largely undefined (Eshghjoo et al., 2021).…”

“…However, the possible role of gut microbiota in the pathogenesis of the kidney disease has been reported (Eshghjoo et al., 2021). Even though, diet is considered a major factor driving the composition and metabolism of the gut microbiota, the effect of dietary supplements on gut microbiota and its mechanistic links to bioactivities are largely undefined (Eshghjoo et al., 2021). Hence, the effect of V. zizanioides as a dietary supplement on microbial enzyme expression in the microbiota is also warranted in future.…”

DNA Methylation Aberrant in Atherosclerosis

“…On the contrary, M2-type usually expresses high levels of anti-inflammatory cytokines, such as interleukin-10 and recombinant human arginase-1, plays an anti-inflammatory role, and predominates in stable plaque and early atherosclerosis ( Tabas and Bornfeldt, 2016 ). A significant hallmark of atherosclerosis is the accumulation of pro-inflammatory metabolites in coronary arteries that respond to pro-atherogenic stimuli, such as free fatty acids (FFAs) and oxidized LDLs (ox-LDLs), and the failure to digest lipids that contribute to the formation of foam cells in atherosclerotic plaques ( Eshghjoo et al, 2021 ).…”