As researchers and clinicians continue their search for new biomarkers capable of predicting cardiovascular event risk, there is optimism that the nontraditional marker trimethylamine N-oxide (TMAO), a microbial byproduct of intestinal bacteria, may serve as an accurate screening tool for predicting future risk of heart attack, stroke, and even death in persons not otherwise identified by traditional risk factors. The TMAO assay, currently available from LipoScience (Raleigh, N.C.) for research only purposes, was recently named by the Cleveland Clinic as one of its top 10 innovations for 2014. TMAO is produced when intestinal bacteria digest the nutrient phosphatidylcholine (choline) present in egg yolks, red meat, and dairy products. This metabolite is believed to directly contribute to the pathophysiology of atherosclerosis and resulting coronary artery disease. A study led by Cleveland Clinic researchers (published in the April issue of the New England Journal of Medicine) established that intestinal microbiota, when suppressed with antibiotics, produce less TMAO, and when not suppressed TMAO was tied to dietary phosphatidylcholine through the use of stable-isotope-tracer feeding studies. Additionally, the study identified the potential clinical significance of the intestinal microbiota-dependent metabolite by showing that fasting plasma TMAO levels predict the risk of future cardiovascular events independently […]
As researchers and clinicians continue their search for new biomarkers capable of predicting cardiovascular event risk, there is optimism that the nontraditional marker trimethylamine N-oxide (TMAO), a microbial byproduct of intestinal bacteria, may serve as an accurate screening tool for predicting future risk of heart attack, stroke, and even death in persons not otherwise identified by traditional risk factors.
The TMAO assay, currently available from LipoScience (Raleigh, N.C.) for research only purposes, was recently named by the Cleveland Clinic as one of its top 10 innovations for 2014.
TMAO is produced when intestinal bacteria digest the nutrient phosphatidylcholine (choline) present in egg yolks, red meat, and dairy products. This metabolite is believed to directly contribute to the pathophysiology of atherosclerosis and resulting coronary artery disease.
A study led by Cleveland Clinic researchers (published in the April issue of the New England Journal of Medicine) established that intestinal microbiota, when suppressed with antibiotics, produce less TMAO, and when not suppressed TMAO was tied to dietary phosphatidylcholine through the use of stable-isotope-tracer feeding studies. Additionally, the study identified the potential clinical significance of the intestinal microbiota-dependent metabolite by showing that fasting plasma TMAO levels predict the risk of future cardiovascular events independently of traditional cardiovascular risk factors, even in low-risk subgroups. Increased plasma levels of TMAO were associated with more than a doubling of risk for a major adverse cardiovascular event.
Given these results, experts are optimistic that by testing the gut biome for cardiovascular risk, doctors soon will be able to personalize nutritional recommendations for their patients to prevent cardiovascular disease based on the production of TMAO, including diet recommendations, using bacteriotherapy (probiotics) to alter the gut microbiota, or potentially to suppress TMAO synthesis through targeted drugs.
LipoScience has developed the TMAO assay in conjunction with the Cleveland Clinic and is currently offering the assay for research use only. Future plans include offering TMAO as a laboratory-developed test on the Vantera Clinical Analyzer, the same nuclear magnetic resonance (NMR)-based diagnostic platform that runs the NMR LipoProfile test.
Takeaway: There is growing interest in utilizing markers generated from gut microbia to predict disease risk, including TMAO, which has been tied to significantly increased risk of a future cardiovascular event.
