Gut microbial metabolites and risk of coronary heart disease: a prospective, multiethnic, metabolomic study

肠道微生物代谢物与冠心病风险:一项前瞻性、多种族、代谢组学研究

基本信息

  • 批准号:
    10214686
  • 负责人:
  • 金额:
    $ 78.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-15 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Gut microbial metabolites have emerged as key players in human cardiometabolic health. In our pilot studies, trimethylamine N-oxide (TMAO) and equol, two diet-derived gut microbial metabolites, were associated with risk of coronary heart disease (CHD), even after adjusting for traditional CHD risk factors. These findings, in line with a growing literature on the importance of gut microbial metabolism in human cardiometabolic health, led to our hypothesis that gut microbial metabolites may be novel biomarkers and/or therapeutic targets for CHD prevention. Yet, to our knowledge, no population-based, prospective studies have applied metabolomics to systematically investigate gut microbial metabolites in relation to risk of CHD, followed by rigorous validation and evaluation of potential diet-microbiota-host interactions. Moreover, only a few studies have examined metabolomic profiles in relation to CHD risk in non-white populations, especially African Americans who bear a disproportionately high burden of CHD. For human gut microbiota research, data from populations of different races/ethnicities, geographic areas, and habitual diets are extremely valuable for determining the causality, generalizability, and clinical utility of potential biomarkers, but are currently lacking. We propose to evaluate circulating microbial metabolites in relation to risk of CHD by leveraging resources from five NIH-funded, population-based, prospective cohorts: The Southern Community Cohort Study (SCCS), Shanghai Women's and Men's Health Studies (SWMHS), Multi-Ethnic Study of Atherosclerosis (MESA), and Atherosclerosis Risk in Communities Study (ARIC). Our study has three aims: Aim 1 (discovery) will use a semi-quantitative assay that detects major groups of microbial metabolites in 900 case-control pairs of blacks, whites, and Asians (300 pairs per race) from the SCCS and SWMHS. Aim 2 (validation) will first use existing metabolomics data in the MESA and ARIC to perform an in-silico validation; confirmed metabolites will then be quantified in an independent set of 1,150 case-control pairs from SCCS, SWMHS, and MESA (~400 pairs per race). We will evaluate whether the associations vary by demographics, and whether microbial metabolites may improve CHD risk prediction. Aim 3 (diet-microbiota-host interaction) will perform a novel mediation- interaction analysis to evaluate whether and to what extent the associations are modified by dietary fiber (as prebiotics) and overall diet quality and modified or mediated by dyslipidemia, hypertension, and diabetes. This will be the first well-powered, multi-ethnic study examining gut microbial metabolites in relation to risk of CHD with careful validation, quantification, and evaluation of diet-microbiota-host interactions. This study will advance our knowledge of the role of gut microbial metabolism in CHD etiology and disparities, identify new biomarkers, and inform novel diet/microbiota-based interventions. Our team has extensive experience in metabolomics and diet-microbiota-CHD research, and thus, is uniquely positioned to accomplish this study.
项目概要 肠道微生物代谢物已成为人类心脏代谢健康的关键参与者。在我们的试点研究中, 三甲胺 N-氧化物 (TMAO) 和牛尿酚这两种饮食来源的肠道微生物代谢物与 冠心病 (CHD) 的风险,即使在调整了传统的 CHD 危险因素后。这些发现,在 与越来越多关于肠道微生物代谢在人类心脏代谢健康中的重要性的文献一致, 导致我们的假设是肠道微生物代谢物可能是新的生物标志物和/或治疗靶点 预防冠心病。然而,据我们所知,还没有基于人群的前瞻性研究应用代谢组学 系统地研究肠道微生物代谢物与冠心病风险的关系,然后进行严格的验证 以及潜在饮食-微生物群-宿主相互作用的评估。此外,只有少数研究探讨了 非白人人群,尤其是患有冠心病的非裔美国人的代谢组学特征与冠心病风险相关 CHD 负担过高。对于人类肠道微生物群研究,来自不同人群的数据 种族/民族、地理区域和习惯饮食对于确定因果关系非常有价值, 潜在生物标志物的普遍性和临床实用性,但目前缺乏。 我们建议通过利用资源来评估与 CHD 风险相关的循环微生物代谢物 来自 NIH 资助的五个基于人群的前瞻性队列:南方社区队列研究 (SCCS), 上海女性和男性健康研究 (SWMHS)、动脉粥样硬化多民族研究 (MESA) 和 社区动脉粥样硬化风险研究 (ARIC)。我们的研究有三个目标: 目标 1(发现)将使用 半定量检测可检测 900 对黑人病例对照中的主要微生物代谢物, 来自 SCCS 和 SWMHS 的白人和亚洲人(每场比赛 300 对)。目标 2(验证)将首先使用现有的 MESA 和 ARIC 中的代谢组学数据用于执行计算机验证;确认的代谢物将被 在来自 SCCS、SWMHS 和 MESA 的一组独立的 1,150 个病例对照对中进行量化(每个病例对照约 400 对) 种族)。我们将评估这些关联是否因人口统计数据而变化,以及微生物代谢物是否 可能会改善冠心病风险预测。目标 3(饮食-微生物群-宿主相互作用)将进行一种新颖的调节- 相互作用分析,以评估这些关联是否以及在何种程度上被膳食纤维改变(如 益生元)和整体饮食质量,并由血脂异常、高血压和糖尿病改变或介导。 这将是第一个强有力的、多种族的研究,检查肠道微生物代谢物与风险的关系 通过仔细验证、量化和评估饮食-微生物群-宿主相互作用来诊断冠心病。这项研究将 增进我们对肠道微生物代谢在 CHD 病因学和差异中的作用的了解,识别新的 生物标志物,并为基于饮食/微生物群的新型干预措施提供信息。我们的团队拥有丰富的经验 代谢组学和饮食微生物群-冠心病研究,因此具有独特的优势来完成这项研究。

项目成果

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Danxia Yu其他文献

Danxia Yu的其他文献

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{{ truncateString('Danxia Yu', 18)}}的其他基金

The Gut Microbiota in Metabolic Surgery: A Multi-Ethnic, Multi-Omic, Longitudinal Study
代谢手术中的肠道微生物群:一项多种族、多组学、纵向研究
  • 批准号:
    10551244
  • 财政年份:
    2021
  • 资助金额:
    $ 78.93万
  • 项目类别:
The Gut Microbiota in Metabolic Surgery: A Multi-Ethnic, Multi-Omic, Longitudinal Study
代谢手术中的肠道微生物群:一项多种族、多组学、纵向研究
  • 批准号:
    10093513
  • 财政年份:
    2021
  • 资助金额:
    $ 78.93万
  • 项目类别:
The Gut Microbiota in Metabolic Surgery: A Multi-Ethnic, Multi-Omic, Longitudinal Study
代谢手术中的肠道微生物群:一项多种族、多组学、纵向研究
  • 批准号:
    10341050
  • 财政年份:
    2021
  • 资助金额:
    $ 78.93万
  • 项目类别:
Gut microbial metabolites and risk of coronary heart disease: a prospective, multiethnic, metabolomic study
肠道微生物代谢物与冠心病风险:一项前瞻性、多种族、代谢组学研究
  • 批准号:
    10654667
  • 财政年份:
    2020
  • 资助金额:
    $ 78.93万
  • 项目类别:
Gut microbial metabolites and risk of coronary heart disease: a prospective, multiethnic, metabolomic study
肠道微生物代谢物与冠心病风险:一项前瞻性、多种族、代谢组学研究
  • 批准号:
    10464885
  • 财政年份:
    2020
  • 资助金额:
    $ 78.93万
  • 项目类别:
Levels of trimethylamine metabolites and their associations with dietary intakes and cardiometabolic biomarkers: the TMAO Pooling Project
三甲胺代谢物的水平及其与饮食摄入量和心脏代谢生物标志物的关联:TMAO 汇集项目
  • 批准号:
    9756226
  • 财政年份:
    2018
  • 资助金额:
    $ 78.93万
  • 项目类别:

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