The contributory role of gut microbiota in cardiovascular disease
W.H. Wilson Tang, Stanley L. Hazen
W.H. Wilson Tang, Stanley L. Hazen
Published October 1, 2014
Citation Information: J Clin Invest. 2014;124(10):4204-4211. https://doi.org/10.1172/JCI72331.
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The contributory role of gut microbiota in cardiovascular disease

Abstract

Our group recently discovered that certain dietary nutrients possessing a trimethylamine (TMA) moiety, namely choline/phosphatidylcholine and L-carnitine, participate in the development of atherosclerotic heart disease. A meta-organismal pathway was elucidated involving gut microbiota–dependent formation of TMA and host hepatic flavin monooxygenase 3–dependent (FMO3-dependent) formation of TMA–N-oxide (TMAO), a metabolite shown to be both mechanistically linked to atherosclerosis and whose levels are strongly linked to cardiovascular disease (CVD) risks. Collectively, these studies reveal that nutrient precursors, gut microbiota, and host participants along the meta-organismal pathway elucidated may serve as new targets for the prevention and treatment of CVD.

Authors

W.H. Wilson Tang, Stanley L. Hazen

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Figure 3

Examples of microbial enzymes that generate TMA, using choline or carnitine as substrates.

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Examples of microbial enzymes that generate TMA, using choline or carnit...
Thus far, 2 distinct microbial enzyme systems have been identified in vitro that can produce TMA from either choline or carnitine as substrate (75, 77). The choline-utilizing enzyme cutC (catalytic polypeptide) and its partner cutD (regulatory polypeptide) make a complex that selectively uses choline as substrate and releases TMA (choline TMA lyase activity). Similarly, a microbial oxygenase (CntA) complexes with the microbial reductase (CntB) to form an active complex that selectively uses carnitine as substrate and forms TMA (carnitine TMA lyase activity). In theory, inhibition of microbial choline and/or carnitine TMA lyases may serve as a potential therapeutic target for CVD through the reduction of microbial TMA and subsequent host TMAO formation.