ABSTRACT/SUMMARY – INTERVENTION CORE Diet is one of the most important determinants of human health and an essential component of population-wide primary prevention strategies. However, there is controversy about the quality and reliability of population- based nutrition research. Indeed, the vast majority of evidence for healthy eating is informed by large studies with dietary patterns assessed via self-report. Self-reported tools have well-recognized limitations. Plasma biomarkers have been a mainstay of epidemiologic studies. Recent advances in metabolomics technology has similarly fostered discovery of metabolites that are highly specific to intakes of foods or food groups. Metabolomics offers a tangible opportunity to identify novel metabolomic signatures for a range of foods and nutrients. However, this progress relies on the tremendous need for controlled feeding studies to identify and validate metabolites specific to each food item and group. Our objective is to establish an Intervention Core, equipped to perform tightly controlled pharmacokinetic and dose-response feeding studies across a range of food items and food groups in diverse populations. We will focus on common foods from the protein and grains food groups: (1) chicken, beef, and soybeans; and (2) whole wheat bread, potatoes, and oats. Based on our collective extensive work in nutrition metabolomics, we hypothesize that acute administration of these foods will have distinct metabolomics signatures that persist over an ensuing 24-hour period. Moreover, plasma concentrations of these metabolites will respond to the amount of the food consumed over a 6-day feeding period. Our long-term goal through these exemplar cases is to establish a rigorous and highly productive resource to the NIH, USDA, and external investigators to systematically catalog specific, reliable, and externally validated metabolomic signatures of nearly all commonly consumed foods in the United States. This proposal combines the nutrition, epidemiology, metabolomics, and feeding trials expertise of investigators at the Harvard T.H.Chan School of Public Health, the Broad Institute of Harvard and MIT, and Harvard Medical School affiliated hospitals to create a state-of-the-art nutrition-metabolomics center that will pave the way for a new era in nutrition research. Building on a long-track record of collaboration, this proposal will contribute novel, objective, metabolomic biomarkers for the characterization of diet in large population- based studies. Ultimately, this proposal answers the NIDDK and USDA’s call “for objective biomarkers of dietary intake that can serve as independent markers of dietary intake and complement current dietary intake assessment methods.”