The Gut Microbiome and Personalized Mediterranean Diet Interventions for Cardiometabolic Disease Prevention

用于预防心血管代谢疾病的肠道微生物组和个性化地中海饮食干预措施

• 批准号: 10275622
• 负责人: Dong Wang
• 金额: $ 76.22万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10275622
• 关键词: 16S ribosomal RNA sequencing; Address; Adherence; Autologous; Biochemical; Biological; Biological Markers; Body Weight; Body Weight decreased; Butyrates; Cardiometabolic Disease; Cardiovascular Diseases; Cohort Studies; Data; Development; Diet; Dietary Intervention; Dietary Lead; Enzymes; Feces; Food; Foundations; Genetic Transcription; Health; Individual; Individual Differences; Intervention; Intervention Studies; Intervention Trial; Israel; Lead; Lipids; Medicine; Mediterranean Diet; Memory; Metagenomics; Microbe; Nature; Non-Insulin-Dependent Diabetes Mellitus; Nutritional Study; Obesity; Outcome; Participant; Persons; Plasma; Population; Prevention; Prevotella; Production; Publishing; Randomized; Randomized Controlled Trials; Recommendation; Reporting; Reproducibility; Research; Research Design; Research Priority; Resolution; Resources; Role; Shotguns; Strategic Planning; Subgroup; TNF gene; Taxonomy; Technology; Testing; Time; Translations; United States National Institutes of Health; Visceral fat; Volatile Fatty Acids; authority; base; biobehavior; burden of illness; cardiometabolic risk; cardiometabolism; cost efficient; design; dietary; disorder prevention; disorder risk; epidemiology study; experience; fasting glucose; fecal transplantation; follow-up; gut microbiome; gut microbiota; improved; individual variation; insight; inter-individual variation; intervention effect; metabolomics; metatranscriptomics; microbial; microbiome research; novel; personalized approach; post intervention; precision nutrition; preservation; prospective; protective effect; response; trimethyloxamine

PROJECT SUMMARY Many authorities recommend the Mediterranean diet (MedDiet) for the prevention of cardiometabolic disease. These dietary recommendations are based on population averages and may not be best suited for a given individual. Preliminary data from our group and others support that a specific dietary intervention may have highly variable effects in different individuals due to the individual composition of the gut microbiome. Furthermore, we recently reported that autologous fecal microbiota transplantation (aFMT) derived from the time of maximal weight reduction enhanced the effects of MedDiet on maintaining cardiometabolic health in an RCT. This background supports our central hypothesis that the gut microbiome can modify the effects of MedDiet on cardiometabolic disease risk. However, no studies have utilized longitudinally collected data from RCTs to test this hypothesis. Most diet-microbiome studies are limited by the use of 16S rRNA gene sequencing yielding only very general taxonomic profiling, thus omitting strain-specific diet-related biochemical functions of microbes. To gain more advanced mechanistic insights, combining shotgun metagenomics and metatranscriptomics and metabolomics in an integrated framework presents a unique opportunity to probe both the composition and functionality of gut microbial communities. This proposed project will leverage two long-term dietary RCTs, the recently completed 18-month DIRECT-PLUS trial of 294 participants and the ongoing 3-year MIND trial of 604 participants, to examine whether individual gut microbial features modify the effects of MedDiet interventions on cardiometabolic risk and body adiposity (Aim 1) and identify metabolites in feces and metabolites in plasma of gut microbial origin that explain inter-individual differences in post-intervention changes in cardiometabolic risk and adiposity (Aim 2) in the DIRECT-PLUS trial. Findings from Aims 1 and 2 will be tested for replication in the MIND trial. In Aim 3, we will investigate long-lasting, post-intervention effects of combined MedDiet and aFMT, and characterize gut microbial changes during and after the interventions in an RCT of 90 participants. Our proposal addresses a major research priority, precision nutrition, emphasized in the 2020–2030 Strategic Plan for NIH Nutrition Research and is directly responsive to PAR-19-377: “Omics-guided Biobehavioral Interventions for Improved Health Outcomes: A Step Forward in Translation” as one of the first efforts to prospectively assess the functional role of gut microbiome in explaining inter-individual heterogeneity in response to dietary interventions. Built on existing biospecimen and data collected in two well-conducted long-term RCTs and state- of-the-art multi'omics technologies, our proposal is a highly cost-efficient opportunity to generate translatable, personalized dietary interventions grounded in reproducible biological mechanisms and contribute to the paradigm shift towards precision nutrition for improved cardiometabolic health.

项目概要 许多权威机构推荐地中海饮食（MedDiet）来预防心脏代谢疾病。 这些饮食建议基于人口平均水平，可能并不最适合特定人群 我们小组和其他人的初步数据支持特定的饮食干预可能具有很高的效果。 由于肠道微生物组的个体组成不同，对不同个体的影响也不同。 最近报道，自体粪便微生物群移植（aFMT）源于最大时间 在一项随机对照试验中，体重减轻增强了 MedDiet 对维持心脏代谢健康的影响。 背景支持我们的中心假设，即肠道微生物组可以改变 MedDiet 对健康的影响 然而，没有研究利用随机对照试验纵向收集的数据来测试。 大多数饮食微生物组研究都受到使用 16S rRNA 基因测序的限制。 非常一般的分类学分析，从而忽略了微生物的菌株特异性、饮食相关的生化功能。 结合鸟枪法宏基因组学和宏转录组学，获得更先进的机制见解 综合框架中的代谢组学提供了一个独特的机会来探究其组成和 该拟议项目将利用两项长期膳食随机对照试验： 最近完成了 294 名参与者的为期 18 个月的 DIRECT-PLUS 试验以及正在进行的 604 名参与者的为期 3 年的 MIND 试验 参与者，检查个体肠道微生物特征是否会改变 MedDiet 干预措施的影响 心脏代谢风险和身体肥胖（目标 1），并鉴定粪便中的代谢物和血浆中的代谢物 肠道微生物起源解释了干预后心脏代谢风险变化的个体间差异 DIRECT-PLUS 试验中的目标 1 和 2 的结果将在试验中进行复制测试。 在 MIND 试验中，我们将研究 MedDiet 和 aFMT 相结合的长期干预后效果， 并描述了 90 名参与者参与的随机对照试验中干预期间和干预后肠道微生物变化的特征。 该提案涉及 2020-2030 年战略计划中强调的一项主要研究重点：精准营养 NIH 营养研究，并直接响应 PAR-19-377：“组学引导的生物行为干预 改善健康结果：转化中的一步”作为前瞻性评估的首批努力之一 肠道微生物组在解释个体间异质性对饮食反应中的功能作用 干预措施建立在现有的生物样本和两项实施良好的长期随机对照试验和国家研究中收集的数据的基础上。 最先进的多组学技术，我们的建议是一个极具成本效益的机会，可以生成可翻译的、 基于可重复的生物机制的个性化饮食干预措施有助于 向精准营养的范式转变，以改善心脏代谢健康。