Identification of trimethylamine N-oxide (TMAO)-producer phenotype is interesting, but is it helpful?

We read with great interest the paper by Wu et al1 reporting on the development of a carnitine challenge test to facilitate the identification of trimethylamine N-oxide (TMAO)-producer phenotype and host-diet-gut dysbiosis. Such a test assumes that, according to a partial reading of the literature, TMAO plays a key role in cardiovascular disease (CVD). Accordingly, the authors assert the implied importance of the potential for adverse CVD-inducing actions of compounds generating TMAO subsequent to the action of gut microbiota on dietary carnitine. However, a more objective reading of the literature shows that the biomedical community is still debating the potential involvement of TMAO in inducing CVD and/or other diseases.2–4 For example, there is substantial evidence that TMAO may not be associated with CVD, and even that low rather than high TMAO levels are associated with CVD and cardiometabolic risk in general. Collins...

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