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.
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DOI：
10.1124/dmd.116.070615
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Shephard EA
中科院分区：
文献类型：
--
作者：
Fennema D;Phillips IR;Shephard EA
含有黄素的单加氧酶3(FMO3)主要是一种参与治疗药物代谢的酶。然而，每天我们都会接触到三甲胺酶(TMA)最丰富的底物之一，这种酶是通过肠道细菌的作用从各种饮食成分中释放出来的。FMO3将有气味的TMA转化为无气味的TMA N-氧化物(TMAO)，并在尿液中排泄。FMO3活性受损会导致遗传性疾病原发性三甲氨基尿症(TMAU)。受影响的人不能产生TMAO，因此排泄大量TMA。肠道细菌的失调可导致继发性TMAU。最近，人们对FMO3及其催化产物TMAO非常感兴趣，因为TMAO与多种影响健康的疾病有关，包括心血管疾病、胆固醇逆向转运和糖脂平衡。在这篇综述中，我们考虑了引起TMA的饮食成分，参与从饮食前体产生TMA的肠道细菌，细菌产生和使用TMA的代谢反应，以及催化反应的酶。还包括有关在口腔和阴道中产生TMA的细菌的信息，这是两个可能影响健康的关键微生物群。最后，我们讨论了TMA/TMAO微生物-主轴在健康和疾病中的重要性，考虑了影响TMA的细菌生产和宿主代谢的因素，TMAO和FMO3在疾病中的参与，以及宿主-微生物轴对TMAU管理的意义。
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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影响因子：
12.2
作者：
Brugère JF;Borrel G;Gaci N;Tottey W;O'Toole PW;Malpuech-Brugère C
通讯作者：
Malpuech-Brugère C
影响因子：
2.6
作者：
Allerston, Charles K.;Shimizu, Makiko;Phillips, Ian R.
通讯作者：
Phillips, Ian R.
影响因子：
6.9
作者：
Boutagy, Nabil E.;Neilson, Andrew P.;Davy, Kevin P.
通讯作者：
Davy, Kevin P.
影响因子：
5.1
作者：
Anesti, V;McDonald, IR;Wood, AP
通讯作者：
Wood, AP
DOI：
10.1016/0304-4165(65)90048-6
发表时间：
1965-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ASATOOR, AM;SIMENHOF.ML
通讯作者：
SIMENHOF.ML