A recent editorial (NEJM 2013; 368: 1647-49) helps explain the link between diet, genes, and gut microbes. This editorial places in context a study, NEJM 2013; 368: 1575-84). “The investigators found than dietary choline is metabolized by gut microbes to trimethylamine (TMA), which in turn is absorbed into the host bloodstream and metabolized in the liver to trimethylamine-N-oxide (TMAO).” TMAO is thought to promote atherogenesis.
The study involved two phases. In the first, using mass spectrometry, before and after suppression of gut microbes with antibiotics, they showed that a phosphatidylcholine challenge increased all choline metabolites; however, antibiotic use suppressed the formation of TMAO.
In the second phase, they looked at fasting plasma TMAO in relation to cardiovascular events in more than 4000 participants who underwent elective coronary angiography. They identified an “independent, dose-dependent relationship between TMAO and the risk of a cardiovascular event.”
TMAO levels depend on the interaction between gut microbial production of TMAO which is affected by diet and by host genetic factors. The genetic factors are related to flavin-containing monooxygenases (FMO1 and FMO3); these enzymes oxidize TMA to TMAO are vary significantly in mice (and probably humans). With regard to diet, by limiting choline-rich foods (see links below regarding choline-rich foods) or by using probiotics, this may limit TMAO production and lower the risk of heart disease.
While these observations are intriguing, the mechanisms of TMAO in causing atherosclerosis and its primary function are unknown and much more information is needed to truly make these findings useful. It is possible that TMAO is simply a biomarker of other factors.
One aside, the editorial states that our gut microbes contain “at least 100 times as many genes as our own genome.”
Take-home message: TMAO is a new potentially modifiable risk factor for atherosclerotic disease.
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