Dietary Biomarkers Development Center at Harvard University

哈佛大学膳食生物标志物开发中心

• 批准号: 10461130
• 负责人: Clary B Clish
• 金额: $ 148.4万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461130
• 关键词: Acute; Area; Avena sativa; Biological Markers; Biomarker of Dietary Intake; Biomedical Research; Bread; Calibration; Carbohydrates; Catalogs; Chickens; Cohort Studies; Crossover Design; Data; Data Analyses; Data Coordinating Center; Diet; Dietary Assessment; Dietary Practices; Dietary intake; Dose; Drug Kinetics; Eating; Ensure; Environment; Faculty; Follow-Up Studies; Food; Food Selections; Fostering; Goals; Health; Health Professional; Hispanic; Hospitals; Hour; Human; Human Characteristics; Human Microbiome; Individual; Institutes; Institution; Intake; Intervention; Leadership; Life Style; Measurement; Measures; Methodology; Methods; Molecular; Multiomic Data; Nurses' Health Study; Nutrient; Nutritional Study; Participant; Physical activity; Plasma; Population; Potato; Proteins; Public Health Schools; Randomized; Recording of previous events; Research Personnel; Resolution; Resource Sharing; Resources; Software Tools; Source; Soybeans; Structure; Study of Latinos; Technology; Testing; Time; Training; Trans-Omics for Precision Medicine; Transducers; United States Department of Agriculture; United States National Institutes of Health; Universities; Urine; Validation; Wheat; Woman; analytical tool; base; beef; biomarker development; biomarker discovery; biomarker performance; biomarker validation; chemical property; cohort; data sharing; data submission; dietary; experience; feeding; food consumption; gut microbiome; improved; indexing; innovation; large datasets; liquid chromatography mass spectrometry; medical schools; metabolome; metabolomics; multidisciplinary; novel; novel marker; nutrition; physical property; precision nutrition; programs; response; tool; validation studies

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.

项目摘要 - 总体而言：对自由生活人群进行准确的饮食评估仍然是一个主要问题 营养研究中的挑战。为了响应 RFA-DK-20-005，我们建议创建膳食生物标志物 哈佛大学的开发中心 (DBDC)。我们的长期目标是建立严谨、高度 生产性资源，可供 NIH、USDA 和外部研究人员使用，以系统地编目经过验证的 美国农业部定义的食物/食物组摄入量的代谢组学特征。我们的具体目标是： 目标 1. 建立行政核心，提供科学领导、行政监督和 无缝协调 DBDC 内部和之间参与核心和项目的工作； 目标 2. 建立执行受控药代动力学 (PK) 和剂量反应的干预核心 喂养研究： 1) 鸡肉、牛肉和大豆； 2）全麦面包、土豆和燕麦。食物 选择是基于它们对美国饮食中蛋白质和碳水化合物摄入量的贡献、它们的潜力 健康影响，以及找到有效标记的希望。尽管如此，我们也愿意测试不同的 与其他 DBDC 和指导委员会协调的食品或食品组； 目标 3. 建立代谢组学核心，该核心将 1) 使用由五个组成部分的集成代谢组学平台 互补的高分辨率和准确的 LC-MS 方法，可全面分析食品- 血浆和尿液中具有不同化学和物理特性的衍生化合物； 2）阐明结构 与食物摄入相关的尚未确定的 LC-MS 代谢物峰； 目标 4. 建立数据分析核心，该核心将： 1) 为所有人提供专门的统计支持和专业知识 中心内的核心和生物标志物项目； 2）管理和维护大型数据集并确保 及时与其他 DBDC 共享分析工具/软件并向数据协调中心提交数据； 目标 5. 通过整合核心资源来开展生物标志物项目，以 1) 表征药代动力学和 使用控制喂养研究的数据建立新型食品生物标志物的校准曲线； 2） 评估已确定的生物标志物在已完成的为期 6 周的控制喂养试验中的表现 三种健康的饮食模式（OmniHeart）； 3) 在两个方面验证已确定的饮食摄入生物标志物 重复测量饮食、营养生物标志物、代谢组和肠道微生物组的观察队列。 哈佛大学提出的 DBDC 结构严谨、高度集成，采用系统性和创新性的方法 饮食生物标志物发现和验证的方法。我们的代谢组学平台已贡献数据 NIH 联盟，包括综合人类微生物组计划 (iHMP)、物理分子传感器 活动联盟 (MoTrPAC) 和精准医学跨组学 (TOPMed) 计划。通过利用 多个领域的专业知识和卓越的资源，我们将为加速发现做出贡献 食品生物标志物，最终目标是推进精准营养研究以改善人类健康。