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
• 负责人: Danxia Yu
• 金额: $ 11.85万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-05 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756226
• 关键词: Affect; Age; American; Animals; Area; Asia; Asians; Atherosclerosis; Beets; Betaine; Bile Acids; Biological Markers; Blood; Blood Pressure; Carbon; Cardiovascular Diseases; Carnitine; Cholesterol; Choline; Cohort Studies; Collaborations; Complex; Consumption; Dairy Products; Data; Development; Diabetes Mellitus; Diet; Dietary intake; Disease; Disease Outcome; Disease Pathway; Domestic Fowls; Dyslipidemias; Edible Plants; Ethnic Origin; Ethnic group; Europe; Exhibits; Extramural Activities; Fabaceae; Female; Fish Products; Fishes; Flavins; Food; Fostering; Foundations; Future; Gender; General Population; Glucose; Gonadal Steroid Hormones; Health; Hispanics; Hospitals; Human; Hypertension; Impaired Renal Function; Individual; Inflammation; Inflammatory; Insulin; Intake; International; Kidney Diseases; Knowledge; Latino; Lead; Learning; Liver; Meat; Mediating; Metabolic Diseases; Metabolism; Mixed Function Oxygenases; Modification; Not Hispanic or Latino; Nuts; Obesity; Participant; Pathway interactions; Play; Population; Population Characteristics; Population Heterogeneity; Population Study; Prevention approach; Prevention strategy; Production; Race; Recording of previous events; Regulation; Renal function; Reporting; Research; Research Personnel; Resources; Risk Factors; Role; Sample Size; Shellfish; Smoking Status; Source; Soy Foods; Spinach - dietary; Statistical Models; Time; Triglycerides; Variant; Vegetables; Wheat; Woman; base; blood lipid; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; career development; cohort; cost efficient; cytokine; egg; epidemiology study; gut microbiota; health disparity; high risk population; inflammatory marker; insight; insulin signaling; lipid metabolism; male; metabolomics; microbial; novel; novel marker; peer; racial and ethnic; recruit; sex; study characteristics; study population; trimethylamine; trimethyloxamine

PROJECT SUMMARY There is a growing appreciation that diet-gut microbiota interactions play an important role in human cardiovascular health. Recent studies have discovered a diet-derived, gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which may promote the development of cardiovascular disease (CVD). So far, only a few small studies among general populations have investigated this novel TMAO-CVD pathway. Limited evidence suggests that TMAO production and metabolism is influenced by both dietary and non-dietary factors, and that the diet-TMAO association may vary across populations due to significant variations in TMAO food sources (e.g., meat vs. fish vs. plant foods). Large-scale, collaborative epidemiologic studies that include ethnically and regionally diverse populations and incorporate comprehensive data on diet, TMAO metabolites, and CVD biomarkers will provide critical insights into this meta-organismal pathway and may pave the way for developing new strategies for CVD prevention and treatment based on diet-gut microbiota interactions. We propose to conduct a large, international, collaborative study: the TMAO Pooling Project. It will be primarily based on the newly established Consortium of Metabolomics Studies (COMETS) and will also include several other population-based studies. As of Oct. 2017, we have recruited 18 studies from the US, Europe, and Asia, bringing a total of 44,164 participants, including 51% women and 46% understudied racial/ethnic groups (i.e., blacks, Hispanic/Latinos, and Asians). Our Specific Aims are: 1) to examine distributions of TMAO and related metabolites (i.e., choline, carnitine, and betaine) across populations by age, sex, region, race/ethnicity, obesity, smoking status, and metabolic disease status; 2) to evaluate associations of TMAO metabolites with intakes of trimethylamine-containing foods including potential variations across populations; and 3) to evaluate associations of TMAO metabolites with known CVD biomarkers (e.g., glucose, blood lipids, and inflammatory markers). We hypothesize that TMAO level may differ across populations due to variations in habitual diets and metabolic disease status, which in turn may affect CVD health in these populations. This will be the first, large-scale, multi-ethnic, multi-national metabolomics study that leverages existing data and consortium resources to investigate this novel diet-TMAO-CVD pathway. It is feasible and extremely time- and cost-efficient. Knowledge gained will help elucidate the distribution, influencing factors, and potential effects of TMAO on CVD. This study will lay a foundation for future studies on the role of diet-gut microbiota interactions in the development of CVD among diverse populations, which may eventually lead to new, population-specific strategies for CVD prevention and treatment via dietary and/or gut microbial modifications. Meanwhile, this study will establish a network for collaborations on emerging topics in CVD research such as gut microbiota, metabolomics, and health disparities, and will foster career development of junior investigators in these areas as they collaborate and learn from senior investigators and their peers.

项目总结 越来越多的人认识到饮食-肠道微生物区系的相互作用在人类 心血管健康。最近的研究发现了一种饮食衍生的依赖肠道微生物区系的代谢物， 三甲胺N-氧化物(TMAO)，可促进心血管疾病(CVD)的发展。到目前为止, 在普通人群中只有几项小型研究调查了这一新的TMAO-CVD途径。有限 有证据表明，TMAO的产生和代谢既受饮食因素的影响，也受非饮食因素的影响， 由于TMAO食物的显著差异，饮食与TMAO的关联可能会因人群而异 来源(例如，肉类、鱼类和植物食品)。大规模、协作的流行病学研究，包括 种族和地区不同的人群，并纳入关于饮食、TMAO代谢物、 而心血管生物标记物将为这一元生物途径提供关键的见解，并可能为 开发基于饮食-肠道微生物区系相互作用的心血管疾病预防和治疗新策略。 我们建议进行一项大型的国际合作研究：TMAO共享项目。会是 主要基于新成立的代谢组学研究联盟(COMET)，还将包括 其他几项以人群为基础的研究。截至2017年10月，我们已经从美国、欧洲、 和亚洲，共有44,164人参加，其中51%是妇女，46%是未充分研究的种族/族裔 群体(即黑人、西班牙裔/拉丁裔和亚裔)。我们的具体目标是：1)检查 TMAO和相关代谢物(即胆碱、肉碱和甜菜碱)按年龄、性别、地区、 种族/民族、肥胖、吸烟状况和代谢性疾病状况；2)评估TMAO的相关性 含三甲胺食物摄入量的代谢物，包括人群间的潜在变异； 以及3)评估TMAO代谢物与已知的心血管生物标志物(例如，葡萄糖、血脂、 和炎症标志物)。我们假设，TMAO水平可能会因种群差异而有所不同 在习惯性饮食和代谢性疾病状态下，这反过来又可能影响这些人群的心血管疾病健康。 这将是第一个大规模、多种族、多国家的代谢组学研究，利用现有的 数据和联盟资源，以研究这一新的饮食-TMAO-CVD途径。这是可行的，也是非常 既省时又省钱。所获得的知识将有助于阐明其分布、影响因素和潜力。 氧化三甲胺对脑血管病的影响本研究将为今后研究饮食-肠道微生物区系的作用奠定基础 不同人群之间在心血管疾病发展中的相互作用，这最终可能导致新的， 通过饮食和/或肠道微生物修饰预防和治疗心血管疾病的针对人群的战略。 同时，这项研究将建立一个关于心血管疾病研究中新出现的主题的合作网络，例如 肠道微生物区系、代谢组学和健康差异，并将促进初级调查人员的职业发展 他们在这些领域开展合作，并向高级调查人员及其同行学习。