Chemical and Biological Liberation of Trimethylamine from Foods

Mitchell, Siân; Zhang, A.Q.; Smith, Robert L.

doi:10.1006/jfca.2002.1068

Cited by 24 publications

(16 citation statements)

References 8 publications

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“…The lack of any increase in urinary TMA or TMAO, in response to ingestion of betaine, in any of the individuals studied ( Zhang et al, 1999 ; Mitchell et al, 2002 ) (see preceding) indicates that the metabolic reactions that produce TMA from betaine, either directly or via dimethylglycine ( Fig. 1 ), or the bacteria in which these reactions occur, are not prevalent, at least in healthy British men.…”

Section: Tma/tmao Host-microbiome Metabolic Axis In Health and Diseasmentioning

confidence: 83%

“…TMAO, the oxygenated product of TMA, is itself a dietary constituent that can give rise to TMA in the gut. Marine fish contain the highest amounts of TMAO (up to 3 mg/g) of any food source ( Mitchell et al, 2002 ). The TMAO is thought to act as an osmolyte that allows adaptation to changes in salinity ( Pang et al, 1977 ) and hydrostatic pressure ( Zerbst-Boroffka et al, 2005 ).…”

Section: Dietary Precursors Of Tma and The Bacteria Involved In Its Pmentioning

confidence: 99%

“…In addition, comparison of the amounts of TMA released by chemical hydrolysis of foods in vitro with those obtained from biologic digestion of the foods in vivo revealed that marine fish and seafood are by far the best source of dietary-derived TMA, with up to 85% of the TMA content of the food being liberated by biologic digestion. In contrast, red meat, despite its high content of carnitine, a good source of TMA when ingested in its pure form, is a relatively poor source of TMA, with only 5% and 12% of the TMA content of lamb and beef, respectively, being released by biologic digestion ( Zhang et al, 1999 ; Mitchell et al, 2002 ). These studies, although on a relatively small number of individuals, indicate that amounts of TMA derived from digestion of a particular food cannot be accurately predicted on the basis of the content of the trimethylamino moiety in the food.…”

Section: Tma/tmao Host-microbiome Metabolic Axis In Health and Diseasmentioning

confidence: 99%

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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

Phillips

Shephard

2016

Drug Metabolism and Disposition

288

234

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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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Section: Tma/tmao Host-microbiome Metabolic Axis In Health and Diseasmentioning

confidence: 83%

Section: Dietary Precursors Of Tma and The Bacteria Involved In Its Pmentioning

confidence: 99%

Section: Tma/tmao Host-microbiome Metabolic Axis In Health and Diseasmentioning

confidence: 99%

See 1 more Smart Citation

Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

Fennema

Phillips

Shephard

2016

Drug Metabolism and Disposition

288

234

View full text Add to dashboard Cite

show abstract

“…Most of the TMA derived from the metabolism of choline and L‐carnitine by bacteria in the gut is absorbed into the bloodstream, and then TMA is rapidly oxidized to TMAO by the hepatic enzyme, flavin‐containing monooxygenase‐3 (FMO3) (Zeisel, ; Zeisel et al, ; Wang et al, ). Saltwater fish contain the highest amounts of TMAO (∼3 g·kg −1 ) of all food sources (Mitchell et al, ).…”

Section: Introductionmentioning

confidence: 99%

Trimethylamine N‐oxide: breathe new life

Subramaniam

Fletcher

2017

British J Pharmacology

143

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“…In addition to their implications for healthy nutrition [125–127], the findings linking microbiota to CVD suggest possible therapeutic approaches. First, since many of the effects of microbiota on CVD (and other disorders) are mediated by metabolites, it may be possible to specifically target their production, transport, or action.…”

Section: Dissecting the Role Of Microbiota In Cvd: The Road Aheadmentioning

confidence: 99%

Unraveling the environmental and genetic interactions in atherosclerosis: Central role of the gut microbiota

2015

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Recent studies have convincingly linked gut microbiota to traits relevant to atherosclerosis, such as insulin resistance, dyslipidemia and inflammation, and have revealed novel disease pathways involving microbe-derived metabolites. These results have important implications for understanding how environmental and genetic factors act together to influence cardiovascular disease (CVD) risk. Thus, dietary constituents are not only absorbed and metabolized by the host but they also perturb the gut microbiota, which in turn influence host metabolism and inflammation. It also appears that host genetics helps to shape the gut microbiota community. Here, we discuss challenges in understanding these interactions and the role they play in CVD.

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Chemical and Biological Liberation of Trimethylamine from Foods

Cited by 24 publications

References 8 publications

Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

Trimethylamine N‐oxide: breathe new life

Unraveling the environmental and genetic interactions in atherosclerosis: Central role of the gut microbiota

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