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

项目总结 许多权威人士推荐地中海饮食(MedDiet)来预防心脏代谢性疾病。 这些饮食建议是基于人口平均水平的，可能并不是最适合给定的 个人的。来自我们小组和其他人的初步数据支持，特定的饮食干预可能会有很高的 由于肠道微生物群的个体组成不同，对不同个体的影响也不同。此外，我们 最近有报道称，自体粪便微生物区系移植(AFMT)起源于 在随机对照试验中，体重减轻增强了MedDiet在维持心脏代谢健康方面的效果。这 背景支持我们的核心假设，即肠道微生物群可以修改MedDiet对 心脏代谢性疾病风险。然而，还没有研究利用从随机对照试验中纵向收集的数据来测试 这个假说。大多数饮食微生物组的研究仅限于使用16S rRNA基因测序 非常一般的分类概况，因此省略了微生物与特定品系饮食相关的生化功能。至 获得更先进的机制洞察力，结合鸟枪式元基因组学和元翻译组学以及 综合框架中的代谢组学提供了一个独特的机会来探索成分和 肠道微生物群落的功能。这个拟议的项目将利用两个长期的饮食RCT，即 最近完成了为期18个月的294名参与者的直接试验和604名正在进行的为期3年的心理试验 参与者，检查个别肠道微生物特征是否改变了MedDiet干预对 心脏代谢风险和身体肥胖(目标1)并识别粪便中的代谢物和血浆中的代谢物 肠道微生物来源解释介入治疗后心脏代谢风险变化的个体差异 和肥胖(目标2)在直接加试验中。AIMS 1和AIMS 2的调查结果将在 心理测试。在目标3中，我们将调查联合使用MedDiet和AFMT的长期、干预后的效果， 并在90名参与者的随机对照试验中描述干预过程中和干预后肠道微生物的变化。我们的 该提案涉及2020-2030年战略计划中强调的一项主要研究重点--精确营养 并直接响应PAR-19-377：“OMICS引导的生物行为干预 《为了改善健康结果：翻译中的进步》作为前瞻性评估的第一批努力之一 肠道微生物组在解释个体间对饮食反应的异质性中的功能作用 干预措施。建立在现有的生物标本和在两个进行良好的长期随机对照试验和州政府收集的数据的基础上- 在最先进的多组学技术中，我们的建议是一个极具成本效益的机会，可以产生可翻译的、 个性化饮食干预以可复制的生物机制为基础，有助于 转向精确营养以改善心脏代谢健康。

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.