Domenico A. Chavez, Marie-Claire Evans, Natalie J. Bohmke, Chandra Bhati, Susan Wolver, Mohammad S. Siddiqui, Danielle L. Kirkman. Virginia Commonwealth University, Richmond, VA.

BACKGROUND: Liver transplant (LT) recipients have an increased risk of cardiovascular disease (CVD), but the underlying mechanisms are not fully understood. In the general population, the gut microbial metabolite trimethylamine n-oxide (TMAO) is associated with atherosclerotic CVD. Physical activity is known to reduce CVD risk, and recent evidence also suggests that exercise can positively modify the gut microbiome. The purpose of this study was to examine the relationship between serum TMAO, vascular endothelial function, and physical activity levels in LT recipients. We hypothesized that higher levels of TMAO would be associated with vascular endothelial dysfunction and low physical activity levels. METHODS: We enrolled 21 LT recipients (11 Female; 6 African American, 1 Asian; Median [Interquartile Range]: Age, 56 [49-64] years; body mass index (BMI), 35.3 [32.1-40.9] kg/m2). Conduit artery endothelial function was assessed by flow-mediated dilation of the brachial artery (FMDBA) with duplex ultrasound. Venous blood samples were analyzed for levels of TMAO by nuclear magnetic resonance spectroscopy. Patients wore accelerometers at the waist for 7 consecutive days, and data were averaged to obtain daily habitual physical activity levels. After evaluation of statistical assumptions, nonparametric associations were assessed using Spearman’s rho. RESULTS: Conduit artery endothelial function (4.09 [3.69-5.50] %) was negatively associated with TMAO (4.73 [2.94-7.81] µM; ρ = -0.49, p = 0.03). TMAO levels were negatively associated with total physical activity (vector magnitude: 262079 [165640-319673] counts; ρ = -0.49, p = 0.03) and time spent in moderate intensity physical activity (19 [10-25] minutes; ρ = -0.44, p = 0.048) but not with daily step counts, sedentary time, or time spent in light physical activity. CONCLUSIONS: Our findings show that higher TMAO levels are associated with worse vascular endothelial function in LT recipients indicating a higher risk for the development of atherosclerotic CVD. Furthermore, higher levels of total and moderate intensity physical activity were associated with lower levels of TMAO. Future LT studies should investigate the efficacy of moderate intensity exercise interventions to improve vascular function by attenuating TMAO. FUNDING: Supported by NIH UL1TR002649

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