1. Gut microbes appear to play a role in producing the metabolite trimethylamine-N-oxide (TMAO) from dietary choline.
2. Elevated fasting TMAO levels are associated with an increased risk of death, stroke or heart attack.
Evidence Rating Level: 2 (Good)
Study Rundown: This group has previously reported data from animal models suggesting that trimethylamine-N-oxide (TMAO) is a proatherogenic dietary metabolite. In this study, they investigate the clinical significance of TMAO in humans. First, they show that gut microbes play a role in TMAO production in humans. Then, they demonstrate an association between TMAO levels and major cardiovascular events in a prospective clinical study.
The finding that antibiotics abolish the rise in TMAO levels after dietary choline intake strongly suggests an obligatory role for the gut microbes in TMAO production. However, the authors could have strengthened this link by characterizing and quantifying the decline in gut microbes after the antibiotic course. Nevertheless, the apparent role of the gut microbes offers new targets for clinical intervention, such as reducing dietary choline intake and inhibiting microbial choline metabolism. The present study also suggests that TMAO may be a useful factor to incorporate into risk models for cardiovascular risk.
In-Depth [prospective study]: In the first part of the study, 40 healthy volunteers were given a dietary phosphatidylcholine challenge consisting of 2 eggs (250mg of choline each) and 250mg of labeled phosphatidylcholine. This challenge led to a rise in plasma TMAO levels. However, this response was eliminated in six volunteers who were given a week-long course of antibiotics (metronidazole and ciprofloxacin) before the phosphatidylcholine challenge. The TMAO response was partially restored a month or more after cessation of antibiotics in these individuals.
In the second part of the study, fasting plasma TMAO levels were measured in 4,007 adults. They were followed for 3 years for major adverse cardiovascular events (death, stroke, myocardial infarction). The unadjusted hazard ratio for major events between the highest-TMAO quartile and the lowest-TMAO quartile was 2.54 (95% confidence interval, 1.96-3.28; p <0.001). This relationship remained significant after controlling for traditional risk factors.
By Tomi Jun and Mitalee Patil
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