Keywords
Trimethylamine N-oxide
Heart diseases
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Abstract
Objective: To examine evidence regarding the relationship between the gut microbiota–TMAO axis and cardiovascular risk, expanding its clinical and pathophysiological relevance. Methods: This is an Integrative Review. The search was conducted in the PubMed, LILACS, and CAPES databases, including articles published between 2016 and 2026, using descriptors related to the topic. Results: Of the 6,408 studies identified, after applying filters, 5 remained, demonstrating the atherosclerotic contribution of trimethylamine N-oxide in cardiovascular pathophysiology in observational studies. Cardiovascular events are associated with elevated TMAO concentrations, whose formation is linked to animal-based dietary patterns. In experimental models, the use of resveratrol (RSV) showed the ability to reduce the synthesis of this compound through remodeling of the gut microbiota, suggesting a protective metabolic effect. Final considerations: In this context, new dietary and pharmacological measures may be considered complementary strategies for individuals at cardiovascular risk. However, further research is essential to evaluate the potential of the TMAO metabolite as a biomarker and to better understand its clinical prognostic role. In addition, further investigations involving RSV should be encouraged, especially regarding its action in modulating the intestinal microbiome with potential impact on the primary and secondary prevention of cardiovascular diseases.
References
AJOOLABADY A, et al. Inflammation in atherosclerosis: Pathophysiology and mechanisms. Cell Death & Disease, 2024; 15: 817.
AMREIN M, et al. Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected coronary artery disease. Clinical Research in Cardiology, 2022; 111(6): 692-704.
CANYELLES M, et al. Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease? International Journal of Molecular Sciences, 2023; 24(3): 1940.
CHEN ML, et al. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism. Journal of Agricultural and Food Chemistry, 2016; 64(25): 5328-5336.
CRIMARCO A, et al. A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults (SWAP-MEAT). The American Journal of Clinical Nutrition, 2020; 112(5): 1188-1199.
GOULART ETV, et al. Microbiota intestinal como novo alvo terapêutico na cardiologia. In: Inovações cardiovasculares: pesquisa, diagnóstico e terapia. Rio de Janeiro-RJ: Editora Epitaya, 2025; 281-289.
GONÇALVES FM. Microbiota e doença cardiovascular. Revista Portuguesa de Hipertensão e Risco Cardiovascular, 2024; 104: 27-32.
HU Y, et al. Bidirectional interactions between resveratrol and gut microbiota: An insight into oxidative stress and inflammatory bowel disease therapy. BioMed Research International, 2019; 2019: 5403761.
JEANDET P. Structure, chemical analysis, biosynthesis, metabolism, molecular engineering, and biological functions of phytoalexins. Molecules, 2018; 23(1): 61.
LI XS, et al. Untargeted metabolomics identifies trimethyllysine, a TMAO-producing nutrient precursor, as a predictor of incident cardiovascular disease risk. JCI Insight, 2018; 3(6): e99096.
LI XS, et al. Trimethyllysine, a trimethylamine N-oxide precursor, provides prognostic value in short- and long-term outcomes in patients with acute coronary syndromes. European Heart Journal, 2019; 40(32): 2700-2709.
LOMBARDO M, et al. Influence of diets based on animal or plant food products on blood and urine levels of trimethylamine-N-oxide (TMAO) in humans. Current Nutrition Reports, 2022; 11(1): 56-68.
MA R, et al. TMAO: A potential mediator of clopidogrel resistance. Scientific Reports, 2021; 11: 6580.
MASIP J, et al. Acute heart failure in the 2021 ESC heart failure guidelines: A scientific statement from the Association for Acute Cardiovascular Care (ACVC) of the European Society of Cardiology. European Heart Journal: Acute Cardiovascular Care, 2022; 11(2): 173-185.
SHARMA A, et al. Plant-based diet versus red meat diet: The finding optimal oral diet-1 randomized cross over trial (FOOD-1). Journal of the American College of Cardiology, 2024; 83(13 Suppl.).
SILVA LV. Investigação de genes e proteínas de bactérias da microbiota intestinal relacionados à regulação da pressão arterial em seres humanos. Dissertação (Mestrado em Biologia Celular e do Desenvolvimento) – Universidade Federal de Santa Catarina, Florianópolis-SC, 2025.
SOUZA MT, SILVA MD, CARVALHO R. Revisão integrativa: o que é e como fazer. Einstein (São Paulo), 2010; 8(1): 102-106.
VALDES AM, et al. The role of the gut microbiota in nutrition and health. BMJ, 2018; 361: k2179.
ZHOU Y, et al. A relação causal entre microbiota intestinal e fibrilação atrial: um estudo de randomização mendeliana de duas amostras. Arquivos Brasileiros de Cardiologia, 2024; 121(11): e20240357.
ZHU W, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 2016; 165(1): 111-124.
ZONG X, et al. Trimethyllysine, a precursor of trimethylamine N-oxide, predicts the presence, severity, and prognosis of heart failure. Frontiers in Cardiovascular Medicine, 2022; 9: 907997.