#9 TMAO ASSAY: Novel Biomaker for the Microbiome

Overview

There is a global hunt in progress using a variety of cardiovascular fingerprints—scientists call them biomarkers—that have been discovered or created to help identify the initiation, development, and ongoing cascade of damage caused by heart disease.

Everyone is familiar with the most common biomarker for heart disease, the blood test for cholesterol levels. In the search for additional ways to predict the risk of heart disease, considerable evidence indicates that a molecule called C-reactive protein (CRP)—a protein made by the blood in response to inflammation of any kind—tends to be elevated in people who go on to develop heart disease and suffer a heart attack.

Scientists have now discovered what may be an important new biomarker for heart disease that serves as an accurate screening tool for predicting future risks of heart attack, stroke, and death in persons not otherwise identified by traditional risk factors and blood tests. The novel biomarker is called TMAO, or trimethylamine N-oxide, and it’s a microbial byproduct of intestinal bacteria.

TMAO is produced when intestinal bacteria digest the nutrient phosphatidylcholine, which is more commonly known as choline. This metabolite is thought to promote atherosclerosis by contributing to cholesterol metabolism in heart artery walls, as well as in the liver and intestines. Major dietary sources of choline include egg yolks, red meat, and dairy products.

Tests of TMAO levels of more than 4,000 adults undergoing angiography over a three-year period recently revealed that TMAO levels are good indicators of who is at risk for serious heart disease—and can also serve as a possible future treatment target. As reported in the New England Journal of Medicine (NEJM) in 2013, those people with the highest levels of TMAO had double the risk of death, nonfatal heart attack, or stroke compared to those with the lowest levels.

While we know how to reduce cholesterol and reduce cardiac risks through diet and exercise, substantial risk for heart disease—the number one killer of American adults—still remains. What this important NEJM study has confirmed is that assessing blood levels of TMAO generated by bacteria in the gut can serve as a powerful tool for predicting future cardiovascular risk, even for those people without known risk factors.

The human gut has about 100 trillion bacteria, and the gut microbial genome, or microbiome, contains 3.3 million genes. By contrast, the human genome contains approximately 23,000 genes. Microbes inhabit our bodies and they play an essential role in digestion. Now, thanks to this recent research, we know that the gut microbiota plays a key role in many diseases outsde the gut, including heart disease.

Heart experts now believe that by testing the gut biome for cardiovascular risk, doctors will be soon be able to personalize nutritional recommendations for their patients on how to best prevent cardiovascular disease based on the production of TMAO. This advice could include modifying the diet to limit the intake of choline-rich food, using bacteriotherapy to alter the gut microbiota with the use of probiotics, or suppresssing TMAO synthesis with a medication. A laboratory test for TMAO research studies is now commercially available.
 

 

Where Are They Now

Along with an increased risk of heart disease, TMAO has now been linked as a biomarker for chronic kidney disease, creating a spiral affect that further increases the risk of heart disease. Research is now being conducted for medications that block the presence of this biomarker in the bloodstream, hoping to eliminate the increased risk for these diseases. In 2016, the only clinical test for measuring TMAO concentration was launched. However, recent study data released in 2016 raises questions about the utility of lowering circulating concentrations of TMAO, via dietary or pharmaceutical approaches, as a means to improve human health.

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