The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
Int Immunopharmacol. 2023 Aug;121:110546. doi: 10.1016/j.intimp.2023.110546. Epub 2023 Jun 24.
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.
肠道微生物群已成为发展和进展心血管疾病 (CVD) 的关键因素。最近的研究强调了微生物代谢产物在调节免疫细胞功能及其对 CVD 的影响中的作用。巨噬细胞在 CVD 的发病机制中具有重要功能，非常容易受到微生物代谢产物的影响。微生物代谢产物，如短链脂肪酸 (SCFA) 和三甲胺 N-氧化物 (TMAO)，与动脉粥样硬化和免疫功能的调节有关。丁酸盐已被证明可减少单核细胞迁移并抑制单核细胞附着在受伤的内皮细胞上，这可能有助于减轻炎症反应和动脉粥样硬化的进展。另一方面，另一种由肠道细菌产生的化合物 TMAO，由于其对脂质代谢和巨噬细胞中胆固醇积累的影响，与动脉粥样硬化有关。色氨酸代谢物吲哚-3-丙酸仅由微生物产生，通过刺激巨噬细胞逆向胆固醇转运 (RCT) 和提高 ABCA1 的表达，被发现可促进动脉粥样硬化的发展。本综述全面讨论了各种微生物产生的代谢产物如何影响 CVD 中的巨噬细胞极化、炎症和泡沫细胞形成。我们还强调了这些影响的机制以及靶向微生物代谢产物治疗 CVD 的潜在治疗应用。
