Lexicon
TMAO
Also known as Trimethylamine N-oxide
Definition
Trimethylamine N-oxide (TMAO) is the main diet-induced metabolite produced by the gut microbiota and is mainly eliminated through renal excretion. [1] TMAO is a low-molecular-weight compound belonging to the class of amine oxides, formed by oxidation of trimethylamine (TMA) by hepatic flavin-containing monooxygenases. [2] TMAO has been widely tested as a prognostic marker across various patient populations, and studies conducted so far support its use as a prognostic marker in cardiovascular disease. [3]
How it works
Most of the TMA derived from gut-bacterial metabolism of choline and L-carnitine is absorbed into the bloodstream and rapidly oxidized to TMAO by the hepatic enzyme flavin-containing monooxygenase-3. [4] TMAO is thought to induce atherosclerosis and thrombosis through effects on lipid metabolism, foam cell formation, endothelial dysfunction, and enhanced platelet reactivity. [5] In chronic kidney disease patients, circulating TMAO concentration shows a strong negative correlation with glomerular filtration rate and a positive correlation with inflammation biomarkers. [6]
Connected concepts
How it's measured
TMAO is measured in body fluids, and its circulating level is determined by factors such as age, sex, diet, gut microbiota composition, kidney function, and hepatic flavin monooxygenase activity. [2] The interpretation of a given TMAO value is complicated because the association between TMAO and outcomes is substantially mediated by renal function, and adjustment for kidney function tends to weaken or reverse it. [1]
What levels mean
Meta-analyses have reported that high circulating TMAO levels are associated with an increased risk of cardiovascular events and all-cause mortality, though the link with cardiovascular disease is not fully consistent. [1] In non-dialysis chronic kidney disease patients, those with the highest circulating TMAO concentration had an increased risk of all-cause mortality (RR 1.26, 95% CI 1.03-1.54), and in non-black dialysis patients the highest TMAO concentration was associated with increased cardiovascular mortality (RR 1.72, 95% CI 1.19-2.47). [6] Elevated circulating TMAO functions as an emerging cardiovascular risk factor, with high levels independently predicting major adverse cardiovascular events and all-cause mortality
Community knowledge
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- 1.Canyelles M, Borràs C, Rotllan N, Tondo M, Escolà-Gil JC, Blanco-Vaca F. Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease? Int J Mol Sci · 2023
- 2.Gatarek P, Kaluzna-Czaplinska J. Trimethylamine N-oxide (TMAO) in human health. EXCLI J · 2021
- 3.Konieczny RA, Kuliczkowski W. Trimethylamine N-oxide in cardiovascular disease. Adv Clin Exp Med · 2022
- 4.Subramaniam S, Fletcher C. Trimethylamine N-oxide: breathe new life. Br J Pharmacol · 2018
- 5.Li Z, He X, Fang Q, Yin X. Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke. Biomolecules · 2024
- 6.Li Y, Lu H, Guo J, Zhang M, Zheng H, Liu Y, Liu W. Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.
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