Predicting Health Outcomes of Mediterranean Diet via Metabolomics of Foods and Biospecimens

通过食物和生物样本的代谢组学预测地中海饮食的健康结果

• 批准号: 9905406
• 负责人: WAYNE W CAMPBELL
• 金额: $ 65.28万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-09 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905406
• 关键词: Address; Antioxidants; Bacteroides; Biochemical; Biological; Biological Markers; Blood; Blood Pressure; Branched-Chain Amino Acids; Carnitine; Chronic Disease; Clinical Research; Clinical Trials; Consumption; Data; Development; Diet; Diet Modification; Dietary Component; Dietary Intervention; Dietary Practices; Dietary intake; Disease; Evaluation; Feces; Fishes; Food; Frequencies; Future; Goals; Health; Health Benefit; Health Promotion; Health Status; Human; Individual; Inductively Coupled Plasma Mass Spectrometry; Inflammation; Intake; Intervention; Intestines; Investigation; Knowledge; Link; Lipids; Liquid substance; Mass Spectrum Analysis; Measurement; Measures; Mediterranean Diet; Metabolic; Metabolic Diseases; Metagenomics; Micronutrients; Mission; Molecular; Molecular Profiling; N-3 polyunsaturated fatty acid; Nutrient; Nutritional; Outcome; Overweight; Pathogenicity; Plasma; Polyunsaturated Fatty Acids; Population; Prevotella; Proteins; Randomized; Recommendation; Research; Sample Size; Sampling; Source; Specimen; Testing; Time; United States National Institutes of Health; Urine; Volatile Fatty Acids; adult obesity; blood lipid; disorder prevention; disorder risk; feeding; gut microbiome; gut microbiota; human subject; improved; innovation; insulin sensitivity; metabolic profile; metabolome; metabolomics; microbiota profiles; novel; post intervention; potential biomarker; prevent; prospective; small molecule; western diet

One of the single most important opportunities to influence an individual's health is through sustained modification of diet. Although certain dietary patterns have clear health benefits or detriments with respect to chronic disease risk, the biochemical and metabolic underpinnings linking such dietary patterns with health effects are not clear. This proposal describes a step-wise strategy whereby the mechanistic effects of individual foods and dietary components on health can be delineated as follows: Step 1) identify molecular signatures of diet/food composites from typical Mediterranean-style (MED) and Westernized diets (WD); Step 2) identify biomarkers of MED and WD exposures in human biospecimens (e.g., plasma, urine, stool); Step 3) connect these signatures and biomarkers with health indicators, including gut microbiome, in human subjects; and Step 4) test these associations in a prospective clinical trial. This proposal leverages already available specimens (blood, urine, stool) from two randomized, controlled feeding trials of MED and WD. Measures of lipid profile, blood pressure, insulin sensitivity, inflammation, and other health indicators are available and will be associated with the comprehensive molecular metabolic profiles generated in this proposal. The central hypothesis is that different dietary patterns (MED vs. WD) will generate distinct food-specific molecular signatures that can be measured in human biospecimens and linked to metabolic health indicators. Guided by strong preliminary data, our hypotheses will be tested in the following specific aims (SA) by using state-of-art foodomics, plasma/urine metabolomics, targeted analysis of known nutrients, and fecal metabolomic/metagenomic approaches to identify and validate molecular signatures in foods and biomarkers in biospecimens (SA 1 and 2); by linking these signatures and biomarkers with health indicators and the gut microbiota (SA 3); and by testing the specific foods or food groups identified in Aims 1-3 that are beneficial to metabolic health in a randomized, prospective, controlled feeding trial (SA 4). The proposed research is significant because, for the first time, it will use a step-wise approach to directly connect a large panel of individual foods and whole diets to metabolic and intestinal health indicators through molecular and metabolic signatures. Results can be used almost immediately to inform future studies. The approach is innovative because it represents a substantial departure from the status quo by examining the nutritional metabolome as part of the broader “exposome” and identifying the overlap between individual foods, composite diets, and biospecimens. Findings from this research will elucidate relationships between dietary exposures and metabolic health by identifying and connecting unique food signatures and biological metabolites. This knowledge will underpin the development of effective and more precise dietary interventions for metabolic disease prevention and recommendations to promote health.

影响个人健康的最重要的机会之一是持续改变饮食，尽管某些饮食模式对慢性疾病风险具有明显的健康益处或危害，但将此类饮食模式与健康影响联系起来的生化和代谢基础却并非如此。该提案描述了一种分步策略，其中单个食物和膳食成分对健康的机械影响可以描述如下：步骤 1) 识别典型地中海风格 (MED) 和西式饮食/食物复合物的分子特征。饮食（WD）；步骤 2）识别人类生物样本（例如血浆、尿液、粪便）中 MED 和 WD 暴露的生物标志物；步骤 3）将这些特征和生物标志物与人类受试者的健康指标（包括肠道微生物组）联系起来； 4）在一项前瞻性临床试验中测试这些关联性，该提案利用了两项随机、对照喂养试验的血脂、血压、胰岛素的现有样本（血液、尿液、粪便）。敏感性、炎症和其他健康指标均可用，并将与本提案中生成的全面分子代谢特征相关联。中心假设是不同的饮食模式（MED 与 WD）将产生不同的食物特异性分子特征。在人类生物样本中进行测量并与代谢健康指标相关联，我们的假设将通过使用最先进的食品组学、血浆/尿液代谢组学、已知营养素的针对性分析，在以下特定目标（SA）中进行测试。和粪便通过代谢组学/宏基因组学方法来识别和验证食品中的分子特征和生物样本中的生物标志物（SA 1 和 2）；通过将这些特征和生物标志物与健康指标和肠道微生物群联系起来（SA 3）；在一项随机、前瞻性、对照喂养试验 (SA 4) 中确定了目标 1-3 中有益于代谢健康的方法。拟议的研究意义重大，因为它将首次使用逐步方法来实现。通过分子和代谢特征直接将大量的单个食物和整体饮食与代谢和肠道健康指标联系起来。结果几乎可以立即用于为未来的研究提供信息，因为它代表了通过检查的现状的重大背离。这项研究的结果将通过识别和连接独特的食物特征和生物代谢物来阐明饮食暴露与代谢健康之间的关系。这些知识将支持开发有效和更精确的饮食干预措施来预防代谢疾病，并提出促进健康的建议。