Document Type


Publication Date


Publication Title

Circulation: Heart Failure


Background—Trimethylamine N-oxide (TMAO), a gut microbe–dependent metabolite of dietary choline and other trimethylamine-containing nutrients, is both elevated in the circulation of patients having heart failure and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerates atherosclerotic lesion development in ApoE-deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the low-density lipoprotein receptor knockout mouse. Methods and Results—C57BL6/J mice were fed either a control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) starting 3 weeks before surgical transverse aortic constriction. Mice were studied for 12 weeks after transverse aortic constriction. Cardiac function and left ventricular structure were monitored at 3-week intervals using echocardiography. Twelve weeks post transverse aortic constriction, myocardial tissues were collected to evaluate cardiac and vascular fibrosis, and blood samples were evaluated for cardiac brain natriuretic peptide, choline, and TMAO levels. Pulmonary edema, cardiac enlargement, and left ventricular ejection fraction were significantly (P<0.05, each) worse in mice fed either TMAO- or choline-supplemented diets when compared with the control diet. In addition, myocardial fibrosis was also significantly greater (P<0.01, each) in the TMAO and choline groups relative to controls. Conclusions—Heart failure severity is significantly enhanced in mice fed diets supplemented with either choline or the gut microbe–dependent metabolite TMAO. The present results suggest that additional studies are warranted examining whether gut microbiota and the dietary choline→TMAO pathway contribute to increased heart failure susceptibility.


This work was supported by grants from the National Heart, Lung, and Blood Institute (National Institutes of Health; 5R01 HL092141, 5R01 HL093579, 1R01 HL11657, and 1U24 HL 094373 to Dr Lefer). This work was also supported by grants P20HL113452, R01HL103866 from the National Heart, Lung, and Blood Institute of the National Institutes of Health and the Office of Dietary Supplements (to Dr Hazen).









Included in

Mathematics Commons