The Role of the Gut Microbiome and Trimethylamine Oxide in Atherosclerosis and Age-Related Disease

The gut microbiome plays a major role in human health, and gut microbial imbalance or dysbiosis is associated with disease development. Modulation in the gut microbiome can be used to treat or prevent different diseases. Gut dysbiosis increases with aging, and it has been associated with the impairment of gut barrier function leading to the leakage of harmful metabolites such as trimethylamine (TMA). TMA is a gut metabolite resulting from dietary amines that originate from animal-based foods. TMA enters the portal circulation and is oxidized by the hepatic enzyme into trimethylamine oxide (TMAO). Increased TMAO levels have been reported in elderly people. High TMAO levels are linked to peripheral artery disease (PAD), endothelial senescence, and vascular aging. Emerging evidence showed the beneficial role of probiotics and prebiotics in the management of several atherogenic risk factors through the remodeling of the gut microbiota, thus leading to a reduction in TMAO levels and atherosclerotic lesions. Despite the promising outcomes in different studies, the definite mechanisms of gut dysbiosis and microbiota-derived TMAO involved in atherosclerosis remain not fully understood. More studies are still required to focus on the molecular mechanisms and precise treatments targeting gut microbiota and leading to atheroprotective effects.

Automated summary

The gut microbiome, particularly its dysbiosis, has a significant impact on human health and disease development. Modulating the gut microbiome has potential for disease prevention and treatment. Dysbiosis increases with age, contributing to gut barrier dysfunction and the release of harmful metabolites such as trimethylamine (TMA). TMA, derived from animal-based food, is oxidized to trimethylamine oxide (TMAO) in the liver and has been associated with several age-related conditions, including peripheral artery disease and vascular aging. Probiotics and prebiotics have shown promise in reducing TMAO levels and atherosclerotic lesions by remodeling the gut microbiota. However, the precise mechanisms and treatments targeting gut dysbiosis and microbiota-derived TMAO in atherosclerosis require further investigation.