Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders. Issue 11 (November 2022)

• Record Type: Journal Article
• Authors: Mudimela, Sowjanya; Vishwanath, Narahari Koppa; Pillai, Anilkumar; Morales, Rodrigo; Marrelli, Sean P.; Barichello, Tatiana; Giridharan, Vijayasree V.
• Is Part Of: Drug discovery today. Volume 27:Issue 11(2022)
• Publication Date: 2022-11
• Subjects: Trimethylamine oxide -- Gut microbiome -- Neurological disorder -- Neuropsychiatric disorder; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2022.08.002
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Trimethylamine N-oxide (TMAO) is a major gut metabolite from dietary phosphatidylcholine. TMAO levels impact oxidative stress, microglial activation, and the apoptosis of neurons. TMAO levels are associated with increased risk of first stroke. TMAO can have neuroprotective or neurodegenerative activities in different conditions. Abstract: 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.