PROJECT SUMMARY - OVERALL: Accurate dietary assessments in free-living populations remain a major challenge in nutrition research. In response to the RFA-DK-20-005, we propose to create a Dietary Biomarkers Development Centers (DBDCs) at Harvard University. Our long-term goal is to establish a rigorous and highly productive resource, available to the NIH, USDA, and external investigators, to systematically catalog validated metabolomic signatures of intakes of foods/food groups defined by the USDA. Our Specific Aims are: Aim 1. Establish an Administrative Core that will provide scientific leadership, administrative oversight, and seamless coordination of the efforts of the participating Cores and Projects within and across DBDCs; Aim 2. Establish an Intervention Core that will perform controlled pharmacokinetic (PK) and dose-response feeding studies of: 1) chicken, beef, and soybeans; and 2) whole wheat bread, potatoes, and oats. The food selection is based on their contributions to protein and carbohydrate intakes in the U.S. diets, their potential health effects, and the promise of finding valid markers. Nonetheless, we are also receptive to testing different foods or food groups in coordination with other DBDCs and the Steering Committee; Aim 3. Establish a Metabolomics Core that will 1) use an integrated metabolomics platform of five complementary high resolution and accurate LC-MS methods that together comprehensively profile food- derived compounds with diverse chemical and physical properties in plasma and urine; 2) elucidate structures of yet unidentified LC-MS metabolite peaks associated with food intake; Aim 4. Establish a Data Analysis Core that will: 1) provide dedicated statistical support and expertise for all Cores and the Biomarkers Project within the Center; and 2) manage and maintain large datasets and ensure timely analytic tool/software sharing with other DBDCs and data submission to the Data Coordinating Center; Aim 5. Conduct a Biomarkers Project by integrating Core resources to 1) characterize pharmacokinetics and establish calibration curves of novel food biomarkers using data from the controlled feeding studies; 2) evaluate the identified biomarkers’ performance in an already completed 6-week controlled feeding trial of three healthy dietary patterns (OmniHeart); and 3) validate the identified dietary intake biomarkers in two observational cohorts with repeated measures of diet, nutrient biomarkers, metabolome, and gut microbiome. The proposed DBDC at Harvard is carefully structured and highly integrated, taking a systemic and innovative approach to dietary biomarker discovery and validation. Our metabolomics platform has contributed data to NIH consortia, including Integrative Human Microbiome Project (iHMP), Molecular Transducers of Physical Activity Consortium (MoTrPAC), and Trans-Omics for Precision Medicine (TOPMed) program. By leveraging multiple areas of expertise and the exceptional resources, we will contribute to the accelerated discovery of food biomarkers, with the ultimate goal of advancing precision nutrition research to improve human health.

PROJECT NARRATIVE We propose to create a state-of-the-art Dietary Biomarker Development Center at Harvard University to systematically catalog validated metabolomic signatures of important food sources of protein and carbohydrates in the US diets. This will be accomplished by combining cutting-edge metabolomics technologies with controlled feeding studies and well-established observational cohorts for the discovery and validations of novel biomarkers of food intake. The findings will contribute to the accelerated discovery of objective and robust dietary biomarkers, thereby facilitating precision nutrition research to improve human health.