Biomarkers Project for the Dietary Biomarkers Development Center at Harvard University

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PROJECT SUMMARY/ABSTRACT – BIOMARKERS PROJECT Accurate dietary assessments are a major challenge in nutritional research, especially among free-living individuals. In contrast to self-reported dietary assessments, dietary biomarkers are more objective and less prone to reporting errors. However, traditional dietary biomarker discovery methods are rate-limiting and rely on prior knowledge of food composition. Advances in metabolomic profiling techniques, coupled with feeding trials, now pave the road for discovering novel food biomarkers more efficiently, although the list of sensitive and specific food biomarkers is still short. In response to the RFA-DK-20-005, this proposal, which is specific for the Biomarkers Project (BP) Core, will focus on the characterization of pharmacokinetics of novel food biomarkers and validation of food biomarkers in both clinical feeding trial and observational study settings in multiple independent populations. Specifically, at Phase 1, based on data and resources to be generated at the Intervention Core, we will calculate half-lives of novel food biomarkers, estimate other pharmacokinetics features of the markers, and establish calibration curves and functions for computing food intake. At Phase 2, we will evaluate changes of food biomarkers following 6-week dietary interventions (DASH-style high- carbohydrate diet, high plant protein diet, and high unsaturated fat diet) implemented in the OmniHeart feeding trial. We will further use multiple markers to construct a diet quality score and examine the effects of the interventions on the score. At Phase 3, we will validate the food biomarkers using dietary data assessed by the gold-standard 7-day diet records and other validated tools in the Lifestyle Validation Study (LVS) and Study of Latinos Nutrition & Physical Activity Assessment Study (SOLNAS). We will further build measurement error correction equations based on the calibration curves and explore inter-relationships between diet, microbiome, and food biomarkers. These proposed projects at the BP Core will significantly accelerate the advances in food biomarker discovery and validation in U.S. populations. In addition, the overall complementary, inter-connected projects proposed for the Harvard Dietary Biomarker Development Center will be led by a highly experienced investigator team consisting of researchers with expertise in feeding trials, metabolomics, bioinformatics, nutritional biomarker research, and nutritional epidemiology. The interdisciplinary expertise and rich, existing resources of multi-ethnic cohorts in the U.S. will lead to significant scientific yields in a cost-effective manner. Data to be generated from the BP Core will not only characterize and validate novel food markers but also build the foundation for applying the food biomarkers in a broad range of research settings, such as evaluation of diet-disease associations or monitoring of dietary compliance. As such, the proposed research has a great potential to advance dietary assessment methodology and to aid in future research toward the development of precision or individualized nutrition strategies for chronic disease prevention and management.