Exploring trimethylamine N-oxide (TMAO) as a metabolic link between obstructive sleep apnea and cardiovascular risk: A cardiometabolic perspective

Obstructive Sleep Apnea (OSA) is a condition that obstructs the upper airway during sleep, inducing intermittent hypoxia that affects the host metabolism, and is associated with gut microbiome dysbiosis. The bidirectional link between host immunometabolism and the cardiovascular system connects with the gut microbiome and has emerged as a research interest in recent years. The gut microbiota is recognized as a potential contributor of OSA related comorbidities, including cardiovascular risk. Recent studies have demonstrated that alterations in gut microbial composition are associated with OSA and intermittent hypoxia. Remarkably, the gut-derived metabolite trimethylamine N-oxide (TMAO) has emerged as a putative metabolic link in OSA-associated cardiometabolic risk. In case of OSA, the dysregulated gut metabolic axis may elevate TMAO, which may contribute to endothelial dysfunction and cardiovascular risk. Interestingly, experimental studies suggest that hepatic flavin-containing monooxygenase 3 (FMO3), which catalyzes TMAO production, may be influenced by hypoxia-responsive metabolic pathways, raising the possibility that OSA could affect not only the gut microbiome but also host enzymatic regulation. This perspective will enhance and promote gut microbial-based sleep research, particularly targeted TMAO for the potential risk assessment and as a cardiometabolic marker in OSA. We propose that TMAO may hold potential as a cardiometabolic biomarker in OSA, warranting further validation.