Abstract
Trimethylamine N-oxide (TMAO) is a molecule generated from choline, betaine, and carnitine via gut microbial metabolism. The plasma level of TMAO is determined by several factors including diet, gut microbial flora, drug administration and liver flavin monooxygenase activity. In humans, recent clinical studies evidence a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events. A direct correlation between increased TMAO levels and neurological disorders has been also hypothesized. Several therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that use TMAO as substrate and the development of target-specific molecules. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies to establish the role of TMAO in human health and disease. In this article, we reviewed dietary sources and metabolic pathways of TMAO, as well as screened the studies suggesting possible involvement of TMAO in the etiology of cardiovascular and neurological disorders, underlying the importance of TMAO mediating inflammatory processes. Finally, the potential utility of TMAO as therapeutic target is also analyzed.
Highlights
There is a growing awareness that intestinal microbial organisms, collectively termed microbiota, participate in the global metabolism of their host [1,2,3], including intestinal health, immune function and/or bioactivation of nutrients and vitamins
Mueller et al, (2015) [47] did an 8 years follow-up study trying to relate plasma trimethylamine N-oxide (TMAO), betaine or choline levels with cardiovascular disease (CVD), but the results showed that the levels were confounded by impaired kidney function or poor metabolic control and they were not associated with presence, incidence or events of coronary heart disease
Recent studies point to the potential contribution of gut microbiota-derived production of TMAO
Summary
There is a growing awareness that intestinal microbial organisms, collectively termed microbiota, participate in the global metabolism of their host [1,2,3], including intestinal health, immune function and/or bioactivation of nutrients and vitamins. More recently microbiota of humans has been linked with complex disease phenotypes such as obesity and insulin resistance [4,5,6]. The potential role of a complex phosphatidylcholine–choline metabolic pathway involving gut microbiota in contributing to the pathogenesis of atherosclerotic coronary artery disease in animal models and humans has been described [7]. A trimethylamine-containing compound and part of the head group of phosphatidylcholine, is metabolized by gut microbiota to produce an intermediate compound known as trimethylamine (TMA). Nutrients 2018, 10, 1398 trimethylamine N-oxide (TMAO). TMAO was thought to be a waste product of choline metabolism without action in our organism but nowadays there is convincing evidence suggesting an association between TMAO and inflammation [8,9,10,11,12]. The exact mechanism underlying this correlation is still unknown
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