Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide (Vaduganathan et al., 2022). In 2011, the gut microbiome was linked to CVD through the metabolite trimethylamine N-oxide (TMAO), which is causally associated with atherosclerosis and reduced cardiac function (Wang et al., 2011). TMAO is formed when gut bacteria metabolize dietary quaternary amines into trimethylamine (TMA), which is then oxidized in the liver. Mitochondrial dysfunction is a hallmark of many forms of CVD, particularly heart failure, where impaired ATP production contributes to exercise intolerance and decreased functional capacity (Zhou & Tian, 2018).
Despite the known associations between TMAO and CVD, its effects on mitochondrial respiration remain poorly defined, and its role in physical performance has not been studied (Makrecka-Kuka et al., 2017; Videja et al., 2021). This thesis investigated the effects of chronic TMAO supplementation on mitochondrial function in cardiac, hepatic, vascular, and skeletal muscle tissues, as well as on physical performance in a murine model. We also examined whether high-intensity interval training (HIIT) could mitigate TMAO accumulation.
Key findings were: (1) HIIT did not reduce plasma TMAO concentrations; (2) TMAO generally did not impair cardiac mitochondrial respiration; and (3) unexpectedly, TMAO improved balance and maximal exercise capacity when combined with exercise.
These results challenge the current understanding of TMAO as solely deleterious and highlight the need for further research. The findings also emphasize the importance of non-pharmacological strategies for managing TMAO levels and improving cardiovascular and functional outcomes.