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: 10289793
• 负责人: Clary B Clish
• 金额: $ 151.21万
• 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/10289793
• 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; Hispanics; 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 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.

项目总结-总体：在自由生活的人群中准确的饮食评估仍然是一个主要的 营养研究的挑战。作为对RFA-DK-20-005的回应，我们建议创建膳食生物标志物 哈佛大学的发展中心。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和外部研究人员使用，以系统地分类验证 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.建立一个行政核心，提供科学的领导，行政监督， 在DBDC内部和之间无缝协调参与核心和项目的工作; 目标2.建立干预核心，进行受控药代动力学（PK）和剂量反应 饲养研究：1）鸡肉、牛肉和大豆; 2）全麦面包、土豆和燕麦。食品 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，以及找到有效标记的承诺。尽管如此，我们也接受测试不同的 与其他DBDC和指导委员会协调食品或食品组; 目标3.建立一个代谢组学核心，将1）使用一个集成的代谢组学平台， 互补的高分辨率和准确的LC-MS方法，共同全面剖析食品- 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 与食物摄入相关的尚未识别的LC-MS代谢物峰; 目标4。建立一个数据分析核心，将：1）为所有人提供专门的统计支持和专业知识 核心和中心内的生物标志物项目; 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。通过整合核心资源开展生物标志物项目，以1）表征药代动力学， 使用控制喂养研究的数据建立新型食物生物标志物的校准曲线; 2） 在已经完成的6周对照喂养试验中评估所鉴定的生物标志物的性能， 三种健康饮食模式（OmniHeart）;以及3）验证两种健康饮食模式中所识别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性队列。 拟议中的哈佛DBDC结构严谨，高度集成，采取了系统和创新的 饮食生物标志物的发现和验证方法。我们的代谢组学平台为以下方面提供了数据： NIH联盟，包括综合人类微生物组项目（iHMP）、物理分子传感器 Activity Consortium（MoTrPAC）和Trans-Omics for Precision Medicine（TOPMed）计划。通过利用 多个领域的专业知识和特殊的资源，我们将有助于加快发现 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。