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: 10649585
• 负责人: Clary B Clish
• 金额: $ 130.3万
• 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/10649585
• 关键词: Acceleration; Acute; Area; Avena sativa; Biological Markers; Biomarker of Dietary Intake; Biomedical Research; Bread; Calibration; Carbohydrates; Catalogs; Chickens; Cohort Studies; Collaborations; Computer software; Crossover Design; Data; Data Analyses; Data Coordinating Center; Dedications; 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; 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; Productivity; Proteins; Public Health Schools; Qualifying; Randomized; Recording of previous events; Research Personnel; Resolution; Resource Sharing; Resources; Source; Soybeans; Structure; Study of Latinos; Technology; Testing; 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; beef; biomarker development; biomarker discovery; biomarker identification; 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：自由生活人群的准确饮食评估仍然是主要的 营养研究挑战。为了响应RFA-DK-20-005，我们建议创建饮食生物标志物 哈佛大学的发展中心（DBDC）。我们的长期目标是建立一个严格而高度的 NIH，USDA和外部研究人员可用于系统验证的生产资源 美国农业部定义的食物/食品群体摄入量的代谢组特征。我们的具体目的是： 目标1。建立一个将提供科学领导，行政监督和的行政核心 无缝协调DBDC内部和跨DBDC的核心和项目的努力； 目标2。建立将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 选择是基于它们在美国饮食中对蛋白质和碳水化摄入量的贡献，它们的潜力 健康效果以及找到有效标记的希望。尽管如此，我们也接受测试不同的 与其他DBDC和指导委员会协调的食品或食品团体； 目标3。建立代谢组学核心，该核心将使用1）使用五个集成的代谢组学平台 完全高分辨率和准确的LC-MS方法，共同介绍食物 - 在血浆和尿液中具有潜水化学和物理特性的化合物； 2）阐明结构 尚未确定的LC-MS代谢产物峰与食物摄入相关； 目标4。建立将：1）为所有人提供专门的统计支持和专业知识的数据分析核心 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。通过将核心资源整合到1）表征药代动力学和 使用受控喂养研究的数据建立新食物生物标志物的校准曲线； 2） 评估了已确定的生物标志物在已经完成的为期6周的受控喂养试验中 三种健康的饮食模式（Omniheart）； 3）在两个 与饮食，养分生物标志物，代谢组和肠道微生物组的重复测量的观察人群。 哈佛大学的拟议DBDC仔细结构并高度整合，采用系统性和创新性 饮食生物标志物发现和验证的方法。我们的代谢组学平台为数据提供了贡献 NIH财团，包括综合人类微生物组项目（IHMP），物理的分子传感器 活动联盟（MOTRPAC）和精密医学（TopMed）计划的跨词。通过利用 多个专业知识和卓越资源领域，我们将为加速发现做出贡献 食品生物标志物，最终的目标是推进精确的营养研究以改善人类健康。