Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders

In the past three decades, research on the gut microbiome and its metabolites, such as trimethylamines (TMA), trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), bile acids, tryptophan and indole derivatives, has attracted the attention of many scientists and industrialists. Among these metabolites, TMAO is produced from dietary choline, phosphatidylcholine, carnitine, and betaine. TMAO and other gut metabolites, such as TMA and SCFAs, reach the brain by crossing the blood-brain barrier (BBB) and are involved in brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age. Several studies have confirmed that altered TMAO levels contribute to metabolic, vascular, psychiatric, and neurodegenerative disorders. This review focuses on how altered TMAO levels impact oxidative stress, microglial activation, and the apoptosis of neurons, and may lead to neuroinflammation, which can subsequently result in the development of psychiatric, cognitive, and behavioral disorders.

Automated summary

Research on the gut microbiome and its metabolites, such as trimethylamines (TMA), trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), bile acids, tryptophan, and indole derivatives, has attracted significant attention in the past three decades. These metabolites, including TMAO, play a role in brain development, neurogenesis, and behavior by crossing the blood-brain barrier (BBB). The composition of the gut microbiota is influenced by various factors, and altered TMAO levels have been associated with metabolic, vascular, psychiatric, and neurodegenerative disorders. This review focuses on the impact of altered TMAO levels on oxidative stress, microglial activation, neuronal apoptosis, neuroinflammation, and the development of psychiatric, cognitive, and behavioral disorders.