Biomarkers Project for the Dietary Biomarkers Development Center at Harvard University

项目摘要/摘要-生物标记物项目 准确的膳食评估是营养学研究中的一大挑战，特别是在自由生活中。 个人。与自我报告的饮食评估相比，饮食生物标记物更客观、更少 容易报告错误。然而，传统的饮食生物标记物发现方法是限速的，并且依赖于 基于食物成分的先验知识。代谢组谱技术与饲喂相结合的研究进展 试验，现在为更有效地发现新的食品生物标志物铺平了道路，尽管敏感的 而特定的食品生物标记物仍然短缺。针对RFA-DK-20-005，这项提案是具体的 对于生物标记物项目(BP)核心，将专注于新食品的药代动力学特征 年临床喂养试验和观察性研究中的生物标记物和食品生物标记物的有效性 多个独立的种群。具体地说，在第一阶段，基于将在 干预核心，我们将计算新型食品生物标志物的半衰期，估计其他药物动力学 标记物的特征，并建立用于计算食物摄入量的校准曲线和函数。在第二阶段， 我们将评估食物生物标记物在6周饮食干预后的变化(DASH式高 碳水化合物饮食、高植物蛋白饮食和高不饱和脂肪饮食)在全心全意喂养中实施 审判。我们将进一步使用多个标记来构建饮食质量评分，并检查 对分数的干预。在第三阶段，我们将使用由 生活方式验证研究(LVS)中的黄金标准7天饮食记录和其他验证工具 拉丁裔营养与体力活动评估研究(SOLNAS)。我们将进一步建立测量误差 基于校准曲线的校正方程，并探索饮食、微生物组、 和食品生物标记物。英国石油公司核心区的这些拟议项目将显著加快食品领域的进展 美国人群中生物标记物的发现和验证。此外，总体上相辅相成，相互联系 为哈佛饮食生物标志物开发中心提出的项目将由一位经验丰富的 研究团队由在喂养试验、代谢组学、生物信息学、 营养生物标记物研究和营养流行病学。跨学科的专业知识和丰富的、现有的 美国多种族群体的资源将以具有成本效益的方式带来显著的科学成果。 BP Core将产生的数据不仅将表征和验证新的食品标记，而且还将 为在广泛的研究环境中应用食品生物标记物奠定基础，如评估 饮食-疾病协会或饮食依从性监测。因此，拟议的研究具有很大的 有潜力推进饮食评估方法，并有助于未来研究开发 精准或个性化的营养策略，用于慢性病预防和管理。

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.