Trimethylamine N-Oxide: The Good, the Bad and the Unknown

Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is det...

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Main Authors: Manuel T. Velasquez, Ali Ramezani, Alotaibi Manal, Dominic S. Raj
Format: Article
Language:English
Published: MDPI AG 2016-11-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/8/11/326
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author Manuel T. Velasquez
Ali Ramezani
Alotaibi Manal
Dominic S. Raj
author_facet Manuel T. Velasquez
Ali Ramezani
Alotaibi Manal
Dominic S. Raj
author_sort Manuel T. Velasquez
collection DOAJ
description Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans.
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spelling doaj.art-15f6b235d3454d6ba73bf045175a66a42022-12-22T02:57:38ZengMDPI AGToxins2072-66512016-11-0181132610.3390/toxins8110326toxins8110326Trimethylamine N-Oxide: The Good, the Bad and the UnknownManuel T. Velasquez0Ali Ramezani1Alotaibi Manal2Dominic S. Raj3Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USADivision of Renal Diseases and Hypertension, The George Washington University School of Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USADivision of Renal Diseases and Hypertension, The George Washington University School of Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USADivision of Renal Diseases and Hypertension, The George Washington University School of Medicine, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USATrimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans.http://www.mdpi.com/2072-6651/8/11/326microbiomedysbiosisuremic toxincardiovascular disease
spellingShingle Manuel T. Velasquez
Ali Ramezani
Alotaibi Manal
Dominic S. Raj
Trimethylamine N-Oxide: The Good, the Bad and the Unknown
Toxins
microbiome
dysbiosis
uremic toxin
cardiovascular disease
title Trimethylamine N-Oxide: The Good, the Bad and the Unknown
title_full Trimethylamine N-Oxide: The Good, the Bad and the Unknown
title_fullStr Trimethylamine N-Oxide: The Good, the Bad and the Unknown
title_full_unstemmed Trimethylamine N-Oxide: The Good, the Bad and the Unknown
title_short Trimethylamine N-Oxide: The Good, the Bad and the Unknown
title_sort trimethylamine n oxide the good the bad and the unknown
topic microbiome
dysbiosis
uremic toxin
cardiovascular disease
url http://www.mdpi.com/2072-6651/8/11/326
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AT aliramezani trimethylaminenoxidethegoodthebadandtheunknown
AT alotaibimanal trimethylaminenoxidethegoodthebadandtheunknown
AT dominicsraj trimethylaminenoxidethegoodthebadandtheunknown