Gut‒heart axis: emerging therapies targeting trimethylamine N-oxide production

Trimethylamine N-oxide (TMAO) has garnered considerable attention because of its role in the pathophysiology and pathogenesis of various disorders, particularly heart and kidney disease. Gut microbes produce trimethylamine (TMA) moieties from common dietary precursors, such as choline or carnitine, which are subsequently metabolized by the liver into TMAO. Circulating TMAO then exerts various effects, influencing dyslipidemia, metabolic syndrome, endothelial dysfunction, and inflammation, as well as other detrimental processes. Many existing medications have been shown to decrease TMAO levels in the blood. However, it remains uncertain whether the improved clinical outcomes offered by these medications are related to the reduction in TMAO levels. Additionally, some of the treatment mechanisms do not directly attack the root problem, so other medications have been developed and trialed. Among this latter group of medications, TMA lyase inhibitors have shown a significant ability to decrease serum TMAO without possessing many theoretical downsides. Studies have demonstrated that these medications improve outcomes, including decreased platelet aggregation, improved blood pressure, enhanced glycemic control, a reduced risk of major adverse cardiac events, and a decrease in the rate of renal dysfunction. Because TMAO is involved in a wide range of disease-related biological processes, further research into new therapies is warranted, with potential implications not only for cardiovascular disease but also for cancer or chronic inflammation conditions as well.