In a study involving data from thousands of people, the risk of a new coronary heart disease diagnosis was statistically associated with bloodstream levels of nine specific molecules that are produced by gut microbes. Danxia Yu of Vanderbilt University Medical Center, U.S., and colleagues present these findings on March 17th in the open-access journal PLOS Medicine.
The human digestive tract naturally contains a large population of microbes. Different people have different proportions of different species of gut microbes, which produce different molecules during their normal, metabolic chemical reactions. These metabolites can enter the bloodstream and exert a broad range of impacts, good and bad, on human health. Some gut microbe metabolites may be linked with a person's risk of coronary heart disease—the world's leading cause of death.
However, the full extent of these potential links remains unclear. To deepen understanding, Yu and colleagues conducted a multi-stage analysis of blood samples from a total of several thousand Black, White, and Asian adults from across the U.S. and Shanghai, China. First, using data from nearly 2,000 of the participants, they discovered several gut microbe metabolites associated with the risk of developing coronary heart disease. Then, they used the rest of the data to validate and refine these links—including external and quantitative validations, and accounting for many other factors known to be associated with risk of coronary heart disease, such as age, family health history, and diet.
The final analysis revealed nine specific gut microbe metabolites in the bloodstream that were associated with a higher or lower chance of developing coronary heart disease. These links remained consistent across some participants when stratified by lifestyle or family history. However, some differences in links between specific metabolites and heart disease risk were found when individuals were stratified by race or age.
This study underscores the link between gut microbes and heart health. On the basis of the findings, the researchers call for follow-up research into the nine metabolites they identified to determine whether they represent potentially promising avenues for development of novel ways to treat or prevent coronary heart disease.
The authors add, "This is one of the most comprehensive metabolomics studies to date, encompassing discovery, in silico validation, and quantitative validation across individuals from diverse ethnic backgrounds and geographic regions. Our findings underscore the importance of gut microbial metabolism in cardiovascular disease development and highlight promising molecules that may serve as novel biomarkers or therapeutic targets for future mechanistic and interventional studies."
In your coverage, please use this URL to provide access to the freely available paper in PLOS Medicine: https://plos.io/46PZAo8
Citation: Zheng Y, Yang JJ, Gupta DK, Herrington DM, Yu B, Nguyen NQH, et al. (2026) Circulating gut microbial metabolites and risk of coronary heart disease: A prospective multi-stage metabolomics study. PLoS Med 23(3): e1004750. https://doi.org/10.1371/journal.pmed.1004750
Author countries: United States of America, United Kingdom
Funding: see manuscript
