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Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease

Fennema, D; Phillips, IR; Shephard, EA; (2016) Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease. Drug Metabolism and Disposition , 44 pp. 1839-1850. 10.1124/dmd.116.070615. Green open access

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Abstract

Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. However, on a daily basis we are exposed to one of the most abundant substrates of the enzyme, trimethylamine, which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous trimethylamine to non-odorous trimethylamine N-oxide, which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria. Affected individuals cannot produce trimethylamine N-oxide and, consequently, excrete large amounts of trimethylamine. A dysbiosis in gut bacteria can give rise to secondary trimethylaminuria. Recently, there has been much interest in FMO3 and its catalytic product trimethylamine N-oxide. This is because trimethylamine N-oxide has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to trimethylamine, the gut bacteria involved in the production of trimethylamine from dietary precursors, the metabolic reactions by which bacteria produce and utilize trimethylamine and the enzymes that catalyze the reactions. Also included is information on bacteria that produce trimethylamine in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the trimethylamine/trimethylamine N-oxide microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of trimethylamine, the involvement of trimethylamine N-oxide and FMO3 in disease and the implications of the host-microbiome axis for management of trimethylaminuria.

Type: Article
Title: Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1124/dmd.116.070615
Publisher version: http://dx.doi.org/10.1124/dmd.116.070615
Language: English
Additional information: Copyright © 2016 The Author(s) This is an open access article distributed under the CC BY Attribution 4.0 International license.
Keywords: flavin-containing monooxygenase/FMO; microbiome
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1494862
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