Abstract
BACKGROUND: Dietary choices can affect human health through alterations in gut microbial metabolism, and gut microbial metabolites could serve as biomarkers for disease risk conferred by dietary intake. However, self-reported dietary intake may not reflect true intake. OBJECTIVES: We identified circulating metabolites, including gut microbiome-related metabolites, associated with adherence to a healthy diet in the ChooseWell 365 study. In this randomized clinical trial, the dietary choices of hospital employees were assessed over 24 mo using not only 24-h dietary recalls but also electronic records of hospital cafeteria purchases. METHODS: Plasma metabolites were profiled from 470 participants. Two targeted metabolomics methods were developed and implemented to expand detection coverage for metabolites related to gut microbial activity. Linear regression models were used to associate metabolites with Healthy Purchasing Scores (HPSs) derived from cafeteria purchases and Healthy Eating Index-2015 (HEI-15) scores derived from dietary recalls. RESULTS: Fourteen metabolites were concordantly associated with the HPS and HEI-15 scores in multivariable models adjusted for age, gender, and race, including the gut microbiome-related metabolites indole-3-propionic acid (HPS, β: 0.16, 95% CI: 0.07, 0.26, P = 7.32 × 10(-4); HEI-15, β: 0.16, 95% CI: 0.07, 0.25, P = 6.79 × 10(-4)), hippuric acid (HPS, β: 0.11, 95% CI: 0.02, 0.21, P = 1.97 × 10(-2); HEI-15, β: 0.10, 95% CI: 0.01, 0.19, P = 3.14 × 10(-2)), and indoxyl sulfate (HPS, β = -0.13, 95% CI: -0.23, -0.03, P = 8.21 × 10(-3); HEI-15, β: -0.12, 95% CI: -0.22, -0.03, P = 8.50 × 10(-3)). These gut microbial metabolites were associated with the intake of specific food groups, such as whole fruits. These metabolites were also associated with clinical variables, including blood pressure, diabetes or prediabetes, and body mass index. CONCLUSIONS: In a secondary analysis of the ChooseWell 365 study, associations between circulating gut microbiome-related metabolites and a healthy diet were confirmed using both objective and subjective measures of consumption. Accurate identification of diet-associated metabolites may help guide dietary or microbiome-based interventions aimed at disease prevention.