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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

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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 1

Nutrient/meta-organismal pathway associated with atherosclerosis and major adverse cardiovascular events.

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Nutrient/meta-organismal pathway associated with atherosclerosis and maj...
Foods rich in cholesterol and fats are also often rich in the indicated dietary nutrients PC (lecithin), choline, and carnitine. Following ingestion, gut microbiota can use these nutrients as a carbon fuel source. While mammals do not have the enzyme, gut microbes have TMA lyases, which can cleave the C-N bond of these nutrients, releasing the TMA moiety as a waste product. Transport via the portal circulation brings the TMA to a cluster of hepatic enzymes, the FMOs (particularly FMO3), that efficiently oxidize TMA, thus forming TMAO. TMAO enters the circulation, where it is predominantly excreted by the kidneys. TMAO has been shown to affect cholesterol and sterol metabolism in animal models, enhancing macrophage cholesterol accumulation and atherosclerosis development. In multiple human studies, elevated TMAO has been independently associated with prevalent CVD and incident risks for MI, stroke, death, and revascularization. [O], oxidation.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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