Jaimez Alvarado S, Flores Enciso MF, Amedei A, Aguirre García MM. Gut microbiota-derived metabolite trimethylamine N-oxide in major adverse cardiovascular events: Mechanisms, risk assessment, and therapeutic strategies. World J Cardiol 2026; 18(3): 116780 [DOI: 10.4330/wjc.v18.i3.116780]
Corresponding Author of This Article
Amedeo Amedei, Full Professor, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3, Florence 50134, Tuscany, Italy. amedeo.amedei@unifi.it
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Mar 26, 2026 (publication date) through Mar 23, 2026
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World Journal of Cardiology
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1949-8462
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Jaimez Alvarado S, Flores Enciso MF, Amedei A, Aguirre García MM. Gut microbiota-derived metabolite trimethylamine N-oxide in major adverse cardiovascular events: Mechanisms, risk assessment, and therapeutic strategies. World J Cardiol 2026; 18(3): 116780 [DOI: 10.4330/wjc.v18.i3.116780]
World J Cardiol. Mar 26, 2026; 18(3): 116780 Published online Mar 26, 2026. doi: 10.4330/wjc.v18.i3.116780
Gut microbiota-derived metabolite trimethylamine N-oxide in major adverse cardiovascular events: Mechanisms, risk assessment, and therapeutic strategies
Samuel Jaimez Alvarado, María Fernanda Flores Enciso, Amedeo Amedei, María Magdalena Aguirre García
Samuel Jaimez Alvarado, María Fernanda Flores Enciso, María Magdalena Aguirre García, Unidad de Investigación UNAM-INC, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 14080, Ciudad de México, Mexico
Amedeo Amedei, Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
Co-corresponding authors: Amedeo Amedei and María Magdalena Aguirre García.
Author contributions: Jaimez Alvarado S, Flores Enciso MF, Amedei A, and Aguirre García MM contributed to review and editing, writing original draft, and conceptualization; Amedei A and Aguirre García MM contributed to funding acquisition and made equal contributions as co-corresponding authors; Aguirre García MM contributed to supervision. All authors approved the final version to publish.
Supported by Dirección General de Asuntos del Personal Académico-Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica, No. IN219025; and Consejo Nacional de Humanidades, Ciencias y Tecnologías, No. CBF2023-2024-734.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Amedeo Amedei, Full Professor, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3, Florence 50134, Tuscany, Italy. amedeo.amedei@unifi.it
Received: November 20, 2025 Revised: December 22, 2025 Accepted: January 29, 2026 Published online: March 26, 2026 Processing time: 123 Days and 8.5 Hours
Abstract
The relationship between trimethylamine N-oxide (TMAO), gut microbiome (GM), and major adverse cardiovascular events (MACE) has gained increasing interest in clinical research. TMAO, a metabolite formed by GM metabolism of dietary nutrients like choline and L-carnitine, has been implicated in the pathogenesis of cardiovascular diseases, including ischemic heart disease, acute myocardial infarction, stroke, and heart failure. Its role in promoting atherosclerosis, endothelial dysfunction, vascular inflammation, and thrombosis highlight its clinical significance. The evidence suggests that unhealthy diet habits and sedentary lifestyles promote GM dysbiosis, which increases TMAO production and MACE risk. Various interventions, like dietary changes, probiotics, and prebiotics, can improve GM to reduce circulating TMAO levels. These approaches show promise in mitigating inflammation and vascular damage associated with cardiovascular diseases. Future research is needed to assess long-term clinical outcomes and establish effective, personalized GM modulation protocols. This review draws upon recent reviewed studies from biomedical databases focusing on TMAO related mechanisms, GM dysbiosis, and MACE risk.
Core Tip: Trimethylamine N-oxide (TMAO) is increasingly proposed as a prognostic biomarker and therapeutic target in cardiovascular disease, yet its clinical signal is strongly shaped by renal function and cardiometabolic comorbidity. We synthesize evidence linking TMAO to risk stratification, including incremental value beyond GRACE in acute coronary syndrome, highlight mechanistic advances from microbiota-targeted trimethylamine-lyase inhibitors, 3,3-dimethyl-1-butanol/fluoromethylcholine, that improve vascular and cardiac phenotypes in preclinical models, and outline a precision-nutrition framework that tailors TMAO-lowering strategies to individual producer metabotypes.
