TMAO in cardiovascular disease: Insights into its value as a biomarker

Abstract Introduction Recent discoveries show that the gut microbiota influences multiple physiological systems outside the gastrointestinal tract, exerting its effects through microbial metabolites. One of the key metabolites involved in these interactions is trimethylamine N-oxide (TMAO), produced from dietary choline predominantly found in animal-derived foods. Elevated TMAO levels have been repeatedly associated with an increased risk of cardiovascular disease (CVD), although its causal contribution in humans remains uncertain. Purpose The objective of this presentation is to summarize existing evidence linking the gut microbiome, TMAO, and cardiovascular disease, and to highlight potential clinical implications. Methods Relevant literature from experimental, translational, and clinical studies was examined, focusing on mechanistic insights, observational data, and preclinical interventions targeting TMAO production or activity. Results Both human and animal studies indicate a clear association between higher TMAO levels and increased cardiovascular risk. In animal models, TMAO administration directly aggravates cardiovascular pathology, while reducing or eliminating TMAO attenuates disease progression—supporting a potential causal link. Direct TMAO-targeting strategies, including trimethylamine (TMA) lyase inhibitors and antisense oligonucleotide therapy, have shown promising results in animal studies but have not yet been evaluated in human trials. Consequently, current strategies to modulate TMAO rely mainly on indirect approaches such as dietary interventions and probiotic supplementation. Conclusion(s) TMAO represents a promising but still incompletely validated biomarker for cardiovascular disease. While preclinical evidence supports a causal role, the lack of well-designed human trials limits translation into clinical practice. Further research is needed to determine whether targeting TMAO could effectively reduce cardiovascular risk and guide personalized therapeutic approaches.