Interpreting circulating microbiome-related metabolites in coronary heart disease
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Why the study?
Are circulating microbiome-related metabolites associated with incident coronary heart disease across diverse populations?
Key Points
- This research examines the role of microbiome-related metabolites as biomarkers for coronary heart disease.
- Conducted a multi-stage study to evaluate microbiome-related metabolites.
- Analyzed circulating metabolites in relation to coronary heart disease.
- Prioritized signals to better understand their implications.
- Identified circulating microbiome-related metabolites linked to coronary heart disease.
- Strengthened the association signal but noted challenges in establishing causality.
Structured PICO
Are circulating microbiome-related metabolites associated with incident coronary heart disease across diverse populations?
P
Population
Participants in five prospective cohorts (SCCS, SWHS/SMHS, ARIC, MESA), including Black Americans, individuals from low-income backgrounds, and Chinese cohorts
I
Intervention
Circulating microbiome-related metabolites (e.g., TMAO, phenylacetylglutamine, imidazole propionate, indole propionate, 3-hydroxybutyrate)
O
Outcome
Incident coronary heart diseasehard clinical
Limitations
- Inability to adjust for kidney function across all primary cohorts
- Residual confounding cannot be excluded
- Inability to establish causality or definitively prove microbial origin of metabolites
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The challenge for a lot of researchers is that cause and effect can be very difficult to prove – we often don't know whether we're seeing a cause or consequence of the problem. It's best to view what you measure in the blood as the first clue, but not definitive.”
YZYulu ZhengResearcher, Vanderbilt University Medical Center
“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.”
Implication
This editorial highlights a multi-stage epidemiologic study that rigorously prioritizes circulating microbiome-related metabolites associated with incident coronary heart disease, while emphasizing the persistent gap between robust association and true causality.
Abstract
Circulating microbiome-related metabolites have emerged as promising biomarkers for coronary heart disease. A recent multi-stage study in PLOS Medicine strengthens signal prioritization but highlights the persistent gap between association and causality.
Discussion
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Cite This Study
Sun et al. (2026) studied this question.