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

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

doi:10.1016/j.drudis.2022.08.002

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

Drug Discov Today. 2022 Nov;27(11):103334. doi: 10.1016/j.drudis.2022.08.002. Epub 2022 Aug 23.

Authors

Sowjanya Mudimela¹, Narahari Koppa Vishwanath¹, Anilkumar Pillai², Rodrigo Morales³, Sean P Marrelli⁴, Tatiana Barichello⁵, Vijayasree V Giridharan⁶

Affiliations

¹ Faculty of Pharmaceutical Sciences, PES University, HN-Campus, Bengaluru, Karnataka, India.
² Pathophysiology of Neuropsychiatric Disorders Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center at Houston (UTHealth), Houston, TX, USA; Research and Development, Charlie Norwood VA Medical Center, Augusta, GA, USA; Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, GA, USA.
³ Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Centro Integrativo de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile.
⁴ Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
⁵ Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center at Houston (UTHealth), Houston, TX, USA; Faillace Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Experimental Physiopathology Laboratory, Graduate Program in Health Sciences, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
⁶ Faillace Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. Electronic address: vijayasree.v.giridharan@uth.tmc.edu.

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,andbetaine. 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.

Keywords: Gut microbiome; Neurological disorder; Neuropsychiatric disorder; Trimethylamine oxide.

Publication types

Review

Grants and funding

RF1 AG072491/AG/NIA NIH HHS/United States