Changes in gut-microbe metabolite linked to heart-disease risk

Last Updated: 2020-02-20

By Anne Harding

NEW YORK (Reuters Health) - Rising levels of the gut-microbe metabolite trimethylamine N-oxide (TMAO) are associated with increased risk of coronary heart disease (CHD) in healthy women, according to new findings from the Nurses' Health Study.

"A plant-based diet may help attenuate such risk," Dr. Lu Qi of Tulane University in New Orleans and Harvard T. H. Chan School of Public Health in Boston told Reuters Health by phone.

TMAO is a marker for atherosclerotic burden, and higher levels have been linked to increased carotid plaque burden and coronary plaque vulnerability, Dr. Qi and his team note in the Journal of the American College of Cardiology.

Choline, L-carnitine and other nutrients found in animal foods are metabolized into trimethylamine (TMA), which is then converted to TMAO in the liver, the authors explain. Changes in diet, including eating less red meat or upping vegetable intake, may affect TMAO production, they add.

In the new study, Dr. Qi and his team looked at longer-term effects of TMAO changes in 760 women who were healthy when they enrolled in the Nurses' Health Study in 1976. All underwent blood collection in 1989-1990 and again in 2000-2002, and were free of heart disease at the second blood collection. The authors identified 380 women who went on to develop CHD during follow-up, which ended in 2016, and matched them to 380 who did not.

CHD risk was highest for women who had the greatest increase in TMAO between the two blood collections (relative risk for top tertile 1.58, P=0.029; RR per standard deviation, 1.33; P=0.013).

Women who were in the top tertile for TMAO levels at both time points were at the highest risk (RR, 1.79, compared with those with low levels at both points).

The relationship between change in TMAO and CHD was most pronounced in the women with the least-healthy diets, based on the Alternate Healthy Eating Index, while healthier eating patterns weakened the association.

Dr. Qi and his team are currently conducting intervention studies of diet and TMAO levels, and recently received funding to look at additional metabolites. "Hopefully we can figure out the precise mechanism linking TMAO and cardiovascular disease and other outcomes in the future," he said.

Dr. Petra Mamic of Stanford University School of Medicine in California, who co-authored an accompanying editorial, noted in a telephone interview with Reuters Health that several compounds have been found to suppress microbial TMAO production.

"These compounds are very nifty in that they can be very specific and not kill the bacteria," she said.

But using diet to improve gut microbiome health is a more "elegant, sustainable" approach, Dr. Mamic added. "We already have, I think, enough data and understanding of what the healthy dietary patterns are, even though it might not be the optimal nutrition for every single person," she said, noting that cardiologists and physicians are already making dietary recommendations to their patients.

"We really need to push for randomized trials of dietary intervention" to fully understand the role of the gut microbiome in cardiovascular health, Dr. Paul A. Heidenreich, also at Stanford and a co-author of the editorial, told Reuters Health by phone.

"The nutritional literature and field has been sorely lacking in actual experiments, and it's almost all observational. We could learn a whole lot more if we could make the effort to actually do true trials of different dietary patterns," he said.

SOURCE: https://bit.ly/38DKUZ6 and https://bit.ly/2P5BdLb Journal of the American College of Cardiology, online February 17, 2020.