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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
Open accessAbstract
Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. On a daily basis, however, we are exposed to one of the most abundant substrates of the enzyme trimethylamine (TMA), which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous TMA to nonodorous TMA N-oxide (TMAO), which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria (TMAU). Affected individuals cannot produce TMAO and, consequently, excrete large amounts of TMA. A dysbiosis in gut bacteria can give rise to secondary TMAU. Recently, there has been much interest in FMO3 and its catalytic product, TMAO, because TMAO 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 TMA, the gut bacteria involved in the production of TMA from dietary precursors, the metabolic reactions by which bacteria produce and use TMA, and the enzymes that catalyze the reactions. Also included is information on bacteria that produce TMA in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the TMA/TMAO microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of TMA, the involvement of TMAO and FMO3 in disease, and the implications of the host-microbiome axis for management of TMAU.
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“Approximately 50% of the ingested TMAO is absorbed unchanged and then excreted in urine. The remaining 50% is converted into TMA in the gut by the action of TMAO reductase [19].”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [19]
In the citing paper
“The degradation of ergothioneine by the enzyme ergothionase produces TMA [19]”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [19]
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Oliphant, K., & Allen-Vercoe, E. (2019) · Microbiome · doi:10.1186/s40168-019-0704-8 · Cited by 1,327
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“Interconversion of lecithin and choline is bidirectional, being the conversion of choline to lecithin catalysed by choline kinase [19] (Figure 1).”
BackgroundInfluential
Metadata
- Authors
- Fennema, D., Phillips, I. R., & Shephard, E. A.
- Affiliations
- Queen Mary University of London (GB)
- Corresponding author
- Shephard, Elizabeth A
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 44
- Issue
- 11
- Pages
- 1839-1850
- ISSN
- 0090-9556 (ISSN-L)
- PMC
- PMC5074467
- OpenAlex
- W2397682060
- Cited by
- 355
- References
- 192
- Citations by year
- 2026: 22 · 2025: 39 · 2024: 48 · 2023: 30 · 2022: 36 · 2021: 56 · 2020: 52 · 2019: 36 · 2018: 20 · 2017: 15
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-12-01)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Drug Metabolism and Disposition (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council (MR/K015494/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- trimethylamine, trimethylamine N-oxide, FMO3, trimethylaminuria, gut microbiota, dietary precursors, oral microbiota, vaginal microbiota, cardiovascular disease, reverse cholesterol transport, glucose and lipid homeostasis
- MeSH terms
- Gastrointestinal Microbiome, Animals, Cardiovascular Diseases, Humans, Methylamines, Oxygenases, Host-Pathogen Interactions
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