Clinical Significance and Potential Role of Trimethylamine N-Oxide in Neurological and Neuropsychiatric Disorders

Authors

Sowjanya Mudimela
Narahari Koppa Vishwanath
Anilkumar Pillai
Rodrigo Morales
Sean P Marrelli
Tatiana Barichello
Vijayasree V Giridharan

Publication Date

11-1-2022

Journal

Drug Discovery Today

Abstract

Research in the last three decades has attracted the attention of many scientists and industrialists on the gut microbiome and its metabolites. Among many of these metabolites, trimethylamine oxide. Dietary choline, phosphatidylcholine, carnitine, and betaine produces TMAO that with other gut metabolites such as TMA (trimethylamine), and short-chain fatty acids (SCFA) enter the circulation. Finally they reach the brain through the blood-brain barrier (BBB) where they are involved in several physiological functions such as brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age resulting in dysbiosis. Several studies have confirmed that altered TMAO levels can be harmful, contributing to several metabolic, vascular, psychiatric and neurodegenerative disorders. This review focuses on how altered TMAO levels impact oxidative stress, microglial activation, and apoptosis of neurons that subsequently lead to the development of psychiatric, cognitive, and behavioral disorders. In addition, possible therapeutic strategies targeting TMAO are discussed.

Keywords

trimethylamine oxide, gut microbiome, neurological disorder, neuropsychiatric disorder

Comments

PMID: 35998800