1Department of Research, Meenakshi Academy of Higher Education and Research
2Department of Oral Medicine and Radiology, Meenakshi Ammal Dental College and Hospital
3Arulmigu Meenakshi College of Nursing, Meenakshi Academy of Higher Education and Research
4Meenakshi College of Allied Health Sciences, Meenakshi Academy of Higher Education and Research
5Meenakshi College of Nursing, Meenakshi Academy of Higher Education and Research
6Meenakshi College of Physiotherapy, Meenakshi Academy of Higher Education and Research
Background: The new evidence indicates that products of gut microbiome metabolism, especially trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs), can have significant effects in regulating inflammation and endothelial activity in vivo and lipid metabolism. Their effects on the future progression of atherosclerotic cardiovascular disease (ASCVD), however, are not very well defined.
Objective: To assess prospective longitudinal relationships between levels of circulating TMAO and SCFA with subclinical and clinical ASCVD 5-year follow-up.
Methods: It was a prospective cohort study on 1,480 adults with known ASCVD risk factors but none of them had a previous cardiovascular event. The levels of plasma TMAO and SCFAs (acetate, propionate, and butyrate) were detected by mass spectrometry on an annual basis. The coronary CT angiography and carotid ultrasound were used to determine atherosclerotic burden at baseline and follow-up. The levels of inflammatory factors, lipid status, and nutrition were followed. Mixed-effects regression assessed the relationships between trajectories of metabolites and plaque progression controlling the effect of demographics, comorbidities, medications, and diet.
Results: An increase in baseline and rising TMAO was independently related to an increase in non-calcified coronary plaque volume every year (β = 0.17, p < 0.001) and an increase in major adverse coronary event incidence (HR 1.42, 95% CI 1.18-1.71). Conversely, an increased level of SCFA was implicated with slower progression of the plaque (β = -0.14, p = 0.004) and a decrease in systemic inflammation and a reduction in the rate of events. The ratios of TMAO/SCFA were strongly predictive of the development of ASCVD.
Conclusion: The microbiome metabolites of the gut have opposite effects on the development of atherosclerotic diseases. High TMAO increases the speed of the formation of plaque, and SCFAs seem to be protective. The results demonstrate the therapeutic impacts of microbiome-specific measures to control ASCVD risk.
Keywords: Gut microbiome, cardiovascular risk, TMAO, inflammation, coronary plaque
How to cite this article: Arunagirinathan N, Poongodi S, Vasanthapriya J, Ramnath V, Jayabharathi B, Parthasarathy R. Role of Gut Microbiome Metabolites (TMAO, SCFA) in Progression of Atherosclerotic Cardiovascular Disease: Longitudinal Study. Int J Drug Deliv Technol. 2026;16(10s): 222-227; DOI: 10.25258/ijddt.16.10s.33
Source of support: Nil.
Conflict of interest: None