Dietary Biomarkers Development Center at Harvard University

项目摘要--总体上：在自由生活的人群中进行准确的饮食评估仍然是一个主要问题 营养学研究中的挑战。为了响应RFA-DK-20-005，我们建议创建一种饮食生物标志物 哈佛大学发展中心(DBDC)。我们的长期目标是建立一个严谨和高度 生产性资源，可供NIH、USDA和外部调查人员使用，以便系统地编目验证 美国农业部定义的食物/食品组摄入量的代谢特征。我们的具体目标是： 目标1.建立行政核心，提供科学的领导、行政监督和 在区域发展中心内部和之间无缝协调参与核心和项目的努力； 目标2.建立干预核心，执行受控药动学(PK)和剂量反应 饲喂研究：1)鸡肉、牛肉和大豆；2)全麦面包、土豆和燕麦。食物 选择是基于他们对美国饮食中蛋白质和碳水化合物摄入量的贡献，他们的潜力 对健康的影响，以及找到有效标记物的承诺。尽管如此，我们也愿意测试不同的 与其他发展区议会和指导委员会协调的食品或食品集团； 目标3.建立代谢组学核心将1)使用一个由五个人组成的综合代谢组学平台 互补的高分辨率和准确的LC-MS方法，结合在一起全面描述食物- 血浆和尿液中具有不同化学和物理性质的衍生化合物；2)阐明结构 与食物摄入量有关的尚未确定的LC-MS代谢物峰； 目标4.建立数据分析核心将：1)为所有人提供专门的统计支持和专业知识 中心内的岩心和生物标志物项目；以及2)管理和维护大型数据集，并确保 及时与其他数据中心共享分析工具/软件，并将数据提交给数据协调中心； 目标5.通过整合核心资源实施生物标记物项目，以1)表征药代动力学和 利用受控喂养研究的数据建立新的食品生物标志物的校准曲线；2) 在已经完成的为期6周的受控喂养试验中评估已确定的生物标志物的性能 三种健康饮食模式(OmniHeart)；以及3)在两种情况下验证已识别的饮食摄入量生物标志物 通过重复测量饮食、营养生物标记物、代谢组和肠道微生物组的观察队列。 哈佛大学拟议的DBDC是精心构建和高度整合的，采取了系统和创新的 膳食生物标记物的发现和验证方法。我们的代谢组学平台已经为 NIH财团，包括整合人类微生物组计划(IHMP)，物理分子传感器 活动联盟(MoTrPAC)和精密医学跨欧米克(TOPMed)计划。通过利用 多个领域的专业知识和非凡的资源，我们将为加速发现 食品生物标志物，最终目标是推进精确营养研究，以改善人类健康。

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.