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性心血管疾病 (CVD) 非常重要，动脉粥样硬化性心血管疾病是一种高度危险的疾病。 这是美国流行的疾病，绝经后妇女的风险尤其高，饮食摄入是一个主要风险。 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。 具体来说，胆碱可以转化为三甲胺，三甲胺 N-氧化物 (TMAO) 的前体， 是一种具有动脉粥样硬化作用的代谢物，这种反应取决于肠道中的细菌。 对这种代谢途径的研究已经检查了富含胆碱的各种食物（即红肉、 然而，总体饮食模式对该途径的影响尚未得到充分研究。 创建了一种新的饮食模式，可以预测 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，一项前瞻性研究 绝经后妇女的队列研究应用 TMAO 饮食模式来研究其之间的关系。 TMAO 产生途径的中间体和血管健康的测量对于获得 更全面地了解总体饮食摄入量对该代谢过程的影响。 个人的脉管系统通常需要侵入性手术，然而，测量视网膜血管口径是 一种在微血管水平上评估个体血管健康状况的非侵入性方法。 提案的目的是研究坚持 TMAO 饮食模式与以下因素之间的关系：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) 使用单独辅助研究的数据进行饮食评估几年后测量视网膜血管口径 我们追求更高程度地坚持 TMAO 饮食模式与 WHI 样本相关。 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 与较低依从性相比的口径测量数据已经收集并可用于代谢组学。 使用液相色谱-质谱法测量血浆样品的概况（>300 种代谢物） 方法以及使用 16S 核糖体 RNA (rRNA) 测序评估肠道微生物组组成 从粪便样本中提取 DNA，并在同一时间点评估习惯性饮食摄入量。 我们已经对数码彩色照片的视网膜血管口径进行了分级。 研究为未来针对血管相关饮食和肠道微生物组的干预措施提供启示 最终根据我们的研究结果，制定了预防动脉粥样硬化的饮食指南。 这项研究可能会增强我提出的培训计划，让我获得更深入的了解。 了解TMAO产生的潜在代谢过程及其对血管健康的影响。 培训计划包括一个多学科团队，这将使我获得营养和生物学研究方面的技能 使用定量和流行病学方法，同时发展我作为独立研究员的职业生涯。