Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk

Apr 24, 2013
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Authors:
Tang WH, Wang Z, Levison BS, et al.
Citation:
N Engl J Med 2013;368:1575-1584.
Summary By:
Daniel T. Eitzman, MD

Study Questions:

Does intestinal microbial metabolism of choline affect cardiovascular (CV) risk?

Methods:

Trimethylamine-N-oxide (TMAO), choline, and betaine levels were measured after a phosphatidylcholine (PC) challenge (two hard-boiled eggs and deuterium [d9]-labeled PC) in healthy participants before and after the suppression of intestinal microbiota with oral antibiotics. The relationship between fasting plasma levels of TMAO and incident CV events (death, myocardial infarction, or stroke) during 3 years of follow-up in 4,007 patients undergoing elective coronary angiography was also determined.

Results:

Time-dependent increases in levels of both TMAO and other choline metabolites were detected after the PC challenge. Plasma levels of TMAO were markedly suppressed after the administration of antibiotics, and then reappeared after withdrawal of antibiotics. Increased plasma levels of TMAO were associated with an increased risk of CV events (hazard ratio for highest vs. lowest TMAO quartile, 2.54; p < 0.001). Elevated TMAO levels predicted an increased risk of CV events after adjustment for traditional risk factors (p < 0.001), as well as in lower-risk subgroups.

Conclusions:

The authors concluded that the production of TMAO from dietary PC is dependent on metabolism by the intestinal microbiota. Also, increased TMAO levels are associated with an increased risk of CV events.

Perspective:

Intestinal microbiota may affect chronic diseases via changes in the metabolome. A recent example related to CV disease is the production of the lecithin metabolite TMAO, which has been shown to be proatherogenic in preclinical studies. The current study establishes the link in humans between dietary PC intake, intestinal microbiota metabolism, TMAO production, and long-term CV risk. An immediate implication from this study is that high dietary intake of PC should be avoided. Whether long-term reduction of plasma TMAO with antimicrobial agents is possible and effective for CV risk reduction will require additional studies.

Keywords: Phosphatidylcholines, Biomarkers, Deuterium, Coronary Angiography, Betaine, Choline


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