Application of a novel dietary pattern predictive of trimethylamine N-oxide production to examine associations with metabolomic profiles, the gut microbiome, and vascular health

应用预测三甲胺 N-氧化物产生的新型饮食模式来检查与代谢组特征、肠道微生物组和血管健康的关联

• 批准号: 10677084
• 负责人: Kaelyn Burns
• 金额: $ 3.94万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677084
• 关键词: 16S ribosomal RNA sequencing; Adherence; Adult; Affect; Age; Ancillary Study; Atherosclerosis; Biological; Biological Markers; Blood Vessels; Caliber; Cardiovascular Diseases; Choline; Circulation; Clinical; Collection; Color; Complex; DNA; DNA sequencing; Data; Development; Diet; Dietary Assessment; Dietary Fiber; Dietary Practices; Dietary intake; Disease; Elderly woman; Epidemiologic Methods; Epidemiologist; Event; Fishes; Food; Future; Genes; Goals; Health; Individual; Intake; Intervention; Measures; Meat; Metabolic Pathway; Metabolism; Methods; National Heart, Lung, and Blood Institute; Nutrient; Nutritional Study; Observational Study; Outcome; Pathway interactions; Plasma; Population; Postmenopause; Prevention; Prevention Guidelines; Procedures; Production; Prospective, cohort study; Protocols documentation; Reaction; Reproducibility; Research; Research Personnel; Retina; Risk Factors; Sampling; Sampling Studies; Standardization; Strategic Planning; Strategic vision; Testing; Time; Training; Unhealthy Diet; United States National Institutes of Health; Woman; Women' s Health; arteriole; biological research; career; dietary guidelines; digital; disorder prevention; egg; experience; gut bacteria; gut microbiome; high risk; high risk men; improved; insight; liquid chromatography mass spectrometry; metabolic abnormality assessment; metabolomics; microbiome composition; modifiable risk; multidisciplinary; novel; nutrient metabolism; older women; precision nutrition; predictive marker; prospective; retina blood vessel structure; skills; stool sample; trimethylamine; trimethyloxamine; venule; young woman

ABSTRACT/PROJECT SUMMARY Good vascular health is important for the prevention of atherosclerotic cardiovascular disease (CVD), a highly prevalent disease in the US, with post-menopausal women at an especially high risk. Dietary intake is a major driver of vascular health, and diet can affect vascular health in part through actions involving the gut microbiome. Specifically, choline can be converted to trimethylamine, a precursor to trimethylamine N-oxide (TMAO) which is a metabolite shown to have atherosclerotic effects. This reaction is dependent on bacteria in the gut microbiome. Studies of this metabolic pathway have examined individual foods rich in choline (i.e., red meat, fish, and eggs), however, the effect of an overall dietary pattern on this pathway has been understudied. We have created a novel dietary pattern predictive of biomarkers of TMAO production (the TMAO dietary pattern) within an ancillary study sample of the Women’s Health Initiative (WHI) Observational Study, a prospective cohort study of post-menopausal women. Applying the TMAO dietary pattern to examine how it is associated with the intermediates of the pathway of TMAO production and a measure of vascular health is critical to gain a more complete understanding of the influence of overall dietary intake on this metabolic process. Examining an individual’s vasculature typically requires invasive procedures, however, measuring the retinal vessel caliber is a noninvasive way to assess an individual’s vascular health at the microvascular level. The purpose of this proposal is to examine how adherence to the TMAO dietary pattern is associated with 1) a broad array of circulating plasma metabolite concentrations, 2) the composition and diversity of the gut microbiome, and 3) retinal vessel caliber measured several years after dietary assessment using data from separate ancillary study samples of the WHI. We hypothesize that higher adherence to the TMAO dietary pattern will be associated with less favorable (e.g., pro-atherogenic) metabolomic profiles, gut microbiome composition, and retinal vessel caliber measures compared to lower adherence. Data are already collected and available on metabolomic profiles (>300 metabolites) of plasma samples measured using liquid chromatography-mass spectrometry methods and on the gut microbiome composition assessed using 16S ribosomal RNA (rRNA) sequencing of DNA extracted from stool samples, with habitual dietary intake assessed at the same time points. Additionally, digital color photographs have already been graded for retinal vessel caliber. We expect findings from this research to provide implications for future interventions targeting the diet and gut microbiome for vascular-related disease prevention. Ultimately, based on our findings, dietary guidelines for the prevention of atherosclerotic CVD may be enhanced. This study will facilitate my proposed training plan by allowing me to gain a deeper understanding of the underlying metabolic process of TMAO production and its influence on vascular health. My training plan includes a multidisciplinary team which will allow me to gain skills in nutrition and biological research using quantitative and epidemiologic methods, while progressing my career as an independent researcher.

摘要/项目摘要 良好的血管健康对于预防动脉粥样硬化心血管疾病（CVD）很重要，这是一种高度 在美国，普遍存在的疾病，绝经后妇女的风险特别高。饮食摄入量是主要的 血管健康的驱动因素和饮食会通过涉及肠道微生物组的作用部分影响血管健康。 具体而言，胆碱可以转化为三甲胺，三甲胺是三甲胺N-氧化物（TMAO）的前体 是一种表现出具有动脉粥样硬化作用的代谢产物。该反应取决于肠道中的细菌 微生物组。该代谢途径的研究检查了富含胆碱的单个食物（即红肉， 但是，已经了解了鱼类和鸡蛋），总体饮食模式对这一途径的影响已被理解。我们 已经创建了一种新颖的饮食模式，可预测TMAO生产的生物标志物（TMAO饮食模式） 在妇女健康计划（WHI）观察性研究的辅助研究样本中， 联赛后妇女的队列研究。应用TMAO饮食模式来检查其如何相关 随着TMAO生产途径的中间体和血管健康的度量对于获得A至关重要 对整体饮食摄入量对这种代谢过程的影响更全面。检查一个 个体的脉管系统通常需要侵入性手术，但是，测量残留的容器口径是 一种评估个人血管健康在微血管水平上的无创方法。这个目的 建议是检查遵守TMAO饮食模式与1）广泛的一系列 循环血浆代谢产物浓度，2）肠道微生物组的组成和多样性，3） 饮食评估几年后使用单独辅助研究的数据测量的视网膜血管口径 whi的样本。我们假设更高对TMAO饮食模式的依从性将与 不太有利（例如，亲动氏源性）代谢组谱，肠道微生物组组成，甚至更多的血管 与较低的依从性相比，口径措施的措施。数据已经收集并在代谢组上可用 使用液相色谱 - 质谱法测量的血浆样品的剖面（> 300代谢产物） 方法和肠道微生物组组成，使用16S核糖体RNA（RRNA）测序评估 从粪便样品中提取的DNA，并在同一时间点评估了习惯性饮食摄入量。此外， 数字彩色照片已经被评级为永久船只口径。我们希望从中发现 研究为针对饮食和肠道微生物组的未来干预措施提供了影响 预防疾病。最终，根据我们的发现，预防动脉粥样硬化的饮食指南 CVD可能会得到增强。这项研究将允许我更深入地提高我提出的培训计划 了解TMAO生产的基本代谢过程及其对血管健康的影响。我的 培训计划包括一个多学科团队，这将使我能够获得营养和生物学研究的技能 使用定量和流行病学方法，同时发展了我作为独立研究人员的职业。