Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy

Abstract

Atherosclerosis is associated with various pathological manifestations, such as ischemic heart disease, ischemic stroke, and peripheral arterial disease, and remains a leading cause of public health concern. Atherosclerosis is an inflammatory disease characterized by endothelial dysfunction; vascular inflammation; and the deposition of lipids, cholesterol, calcium, and cellular debris within the vessel wall intima. In-depth studies of gut flora in recent years have shown that bacterial translocation and the existence of bacterial active products in blood circulation can affect the inflammatory state of the whole blood vessel. The gut flora is considered to be a large “secretory organ,” which produces trimethylamine-N-oxide (TMAO), short-chain fatty acids and secondary bile acids by breaking down the ingested food. Studies have shown that TMAO is an independent risk factor for the occurrence of malignant adverse cardiovascular events, but whether it is harmful or beneficial to patients with cardiovascular diseases with mild or no clinical manifestations remains controversial. We review the relationship between TMAO and its precursor (L-carnitine) and coronary atherosclerosis and summarize the potential molecular mechanism and therapeutic measures of TMAO on coronary atherosclerosis.

The Nutrition-Microbiota-Physical Activity Triad: An Inspiring New Concept for Health and Sports Performance

“…This waste product produced by the microbiota can pass into the bloodstream. It is then oxidized by the liver to trimethylamine-N-oxide, a substance that promotes the formation of atherosclerotic plaques [ 42 , 43 ].…”

Lipid Profile Is Negatively Associated with Uremic Toxins in Patients with Kidney Failure—A Tri-National Cohort

“…To the best of our knowledge, a link between lipid metabolism and PAG has not been previously reported. In contrast, most published evidence suggest a direct stimulation of adverse cholesterol metabolism by the uremic toxin TMAO [32]. In accordance, inhibiting TMAO production by a knockdown of hepatic flavin-containing monooxygenase 3 entirely prevents the development of dyslipidemia and atherosclerosis in mice [33].…”

Dietary compounds in modulation of gut microbiota-derived metabolites

“…After absorption, TMA can be oxidized to trimethylamine N-oxide TMAO under the action of hepatic flavin-containing monooxygenases (FMOs) such as FMO1 and FMO3 ( 120 ). Increased TMAO then promotes oxidative stress and inflammation of endothelial cells, activates the inflammasome NOD-like receptor protein 3 and nuclear factor kappa B signaling in vascular smooth muscle cells, promotes the transformation of macrophages into foam cells, promotes platelet hyperreactivity, and alters cholesterol transport and bile acid synthesis ( 121 ). Correspondingly, high level of blood TMAO might contribute to heart disease, diabetes, atherosclerosis, and even cancer ( 122 , 123 ).…”