Roles of Trimethylamine-N-oxide in Atherosclerosis and Its Potential Therapeutic Aspect: A Literature Review

Abstract

Current research supports the evidence that the gut microbiome (GM), which consist of gut microbiota and their biologically active metabolites, is associated with atherosclerosis development. Trimethylamine-N-oxide (TMAO), a metabolite produced by the GM through trimethylamine (TMA) oxidation, significantly enhances the formation and vulnerability of atherosclerotic plaques. TMAO promotes inflammation and oxidative stress in endothelial cells, leading to vascular dysfunction and plaque formation. Dimethyl-1-butanol (DMB), iodomethylcholine (IMC) and fluoromethylcholine (FMC) have been recognized for their ability to reduce plasma TMAO by inhibiting trimethylamine lyase, a bacterial enzyme involved in the choline cleavage anaerobic process, thus reducing TMA formation. Conversely, indole-3-carbinol (I3C) and trigonelline inhibit TMA oxidation by inhibiting flavin-containing monooxygenase-3 (FMO3), resulting in reduced plasma TMAO. The combined use of inhibitors of choline trimethylamine lyase and flavin-containing monooxygenase-3 could provide novel therapeutic strategies for cardiovascular disease prevention by stabilizing existing atherosclerotic plaques. This review aims to present the current evidence of the roles of TMA/TMAO in atherosclerosis as well as its potential therapeutic prevention aspects.

Role of the gut microbiota in complications after ischemic stroke

“…LPS receptors CD14 and Fc g III receptor CD16 + monocytes are a subgroup with specific pro-inflammatory functions; blood TMAO concentration is positively related to the level of pro-inflammatory intermediate CD14 ++ CD16 + monocytes (Yang et al, 2023). Intermediate CD14 + + CD16 + monocytes secrete a large amount of inflammatory cytokines, such as TNF-a, to promote inflammatory responses (Oktaviono et al, 2023). The high expression of adhesion molecules, such as CD162/P-selectin glycoprotein ligand-1 (PSGL-1) and myeloperoxidase, the primary source of reactive oxidants in the innate immune response, in intermediate monocytes contributes to their thrombogenic and atherogenic properties (Wildgruber et al, 2016).…”