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/项目总结 良好的血管健康对于预防动脉粥样硬化性心血管疾病（CVD）是重要的， 这种疾病在美国很流行，绝经后妇女的患病风险尤其高。饮食摄入是一个主要的 血管健康的驱动因素，饮食可以部分通过涉及肠道微生物组的作用影响血管健康。 具体地，胆碱可以转化为三甲胺，其是N-氧化三甲胺（TMAO）的前体， 是一种具有动脉粥样硬化作用的代谢物。这种反应依赖于肠道中的细菌 微生物组对这种代谢途径的研究已经检查了富含胆碱的个别食物（即，红肉， 鱼和蛋），然而，总体饮食模式对这一途径的影响尚未得到充分研究。我们 创造了一种新的饮食模式，可预测TMAO产生的生物标志物（TMAO饮食模式） 在妇女健康倡议（WHI）观察性研究的辅助研究样本中， 绝经后妇女的队列研究。应用TMAO饮食模式来研究它是如何与 与TMAO生产途径的中间体和血管健康的措施是至关重要的，以获得一个 更全面地了解整体饮食摄入对代谢过程的影响。截查一辆 个体的脉管系统通常需要侵入性程序，然而，测量视网膜血管口径是不可能的。 一种在微血管水平评估个体血管健康的非侵入性方法。这样做的目的 建议是研究如何坚持TMAO饮食模式与1）广泛的 循环血浆代谢物浓度，2）肠道微生物组的组成和多样性，以及3） 使用来自独立辅助研究的数据，在饮食评估后数年测量视网膜血管口径 WHI的样本。我们假设，更高的坚持TMAO饮食模式将与 不太有利的（例如，促动脉粥样硬化）代谢组学特征、肠道微生物组组成和视网膜血管 口径措施相比，较低的坚持。已经收集了代谢组学的数据， 使用液相色谱-质谱法测量的血浆样品的图谱（>300种代谢物） 方法和使用16 S核糖体RNA（rRNA）测序评估的肠道微生物组组成 从粪便样本中提取的DNA，在同一时间点评估习惯性饮食摄入量。此外，本发明还 数字彩色照片已经针对视网膜血管口径进行了分级。我们期待从这一发现 研究为未来针对饮食和肠道微生物组的血管相关干预提供了启示 疾病预防。最终，根据我们的发现，预防动脉粥样硬化的饮食指南 CVD可以增强。这项研究将有助于我提出的培训计划，让我获得更深的 了解TMAO产生的潜在代谢过程及其对血管健康的影响。我 培训计划包括一个多学科的团队，这将使我获得营养和生物研究方面的技能 使用定量和流行病学的方法，同时作为一个独立的研究者发展我的职业生涯。