Metabolomics signatures underlying diet, lifestyle and gut microbiota for diabetes

摘要/摘要 血液代谢组学分析可以检测到代谢的细微变化，这些变化可能预示着后者 2型糖尿病(T2D)的发展。这既可以揭示通向T2D的早期步骤，也可以 提供一种新的工具来识别高危个人。拉美裔/拉美裔，美国规模最大、增长最快的国家 与非西班牙裔白人相比，少数民族人群的糖尿病患病率高出66%。我们 拉美裔/拉丁裔在生物学和社会文化特征上各不相同，因此可能有不同的饮食习惯， 生活方式和肠道微生物区系模式可能影响与T2D有关的代谢物。这样做的主要目标是 项目是确定T2D风险的代谢组学特征，并检查饮食、生活方式和肠道微生物区系 影响与T2D相关的代谢组学特征。特别是，我们建议执行高吞吐量 1000对T2D的血浆代谢组学分析(400种已知代谢物和数百种未知代谢物) 拉美裔社区健康研究(SOL)中的事件病例和配对对照 美国拉美裔/拉丁裔中与事件T2D相关的新代谢组学特征。在索尔，我们将 利用现有的大量实验室测量数据(例如空腹血糖和胰岛素、糖化血红蛋白和2小时 口服葡萄糖耐量试验后)和客观测量的行为(例如，加速度法、生物标志物- 测量的饮食因素)与T2D相关。利用来自正在进行的肠道微生物组的肠道微生物组数据 在Sol项目中，我们将表征肠道微生物组成和相关功能特征 血浆代谢组学与T2D有关，并检查饮食在调节肠道微生物区系中的作用 相关代谢物。T2D中涉及的代谢组学特征将在非西班牙裔队列中进一步检查 通过纳入1,500对T2D事件病例和来自护士健康研究(NHS)和 卫生专业人员随访研究(HPFS)，两项正在进行的前瞻性队列研究，具有相同的 代谢组学图谱平台、肠道微生物组数据以及客观测量的饮食和生活方式因素。这个 同时纳入西班牙裔和非西班牙裔队列可能会为饮食/生活方式、肠道的作用提供独特的见解 微生物区系，以及T2D发育过程中的代谢途径。这些发现可能会有很大的潜力 确定T2D预防和干预的新目标。

Summary/Abstract Metabolomics profiling of blood can detect subtle changes in metabolism that may presage the later development of type 2 diabetes (T2D). This can both reveal early steps in the pathway to T2D, and also provide a novel tool to identify high risk individuals. Hispanics/Latinos, the largest and fastest growing US minority population, have a 66% higher prevalence of diabetes compared to non-Hispanic whites. US Hispanics/Latinos are diverse in biological and sociocultural characteristics, and thus may have distinct diet, lifestyle and gut microbiota patterns which likely influence metabolites implicated in T2D. The Main Goal of this project is to identify metabolomics signatures for T2D risk and examine how diet, lifestyle and gut microbiota influence metabolomics profiles associated with T2D. In particular, we propose to perform high-throughput metabolomics profiling (>400 known and hundreds of unknown metabolites) of plasma from 1000 pairs of T2D incident cases and matched controls in the Hispanic Community Health Study of Latinos (SOL) to identify novel metabolomics signatures associated with incident T2D in US Hispanics/Latinos. In the SOL, we will leverage existing extensive data on laboratory measures (e.g. fasting glucose and insulin, HbA1c, and 2-hr post oral glucose tolerance test) and objectively measured behaviors (e.g., accelerometry, biomarker- measured dietary factors) relevant to T2D. Utilizing gut microbiome data from an ongoing gut microbiome project in the SOL, we will characterize gut microbial composition and functional features associated with plasma metabolomics profiles implicated in T2D and examine the role of diet in modulating gut microbiota- related metabolites. Metabolomics profiles implicated in T2D will be further examined in non-Hispanic cohorts by including 1,500 pairs of T2D incident cases and matched controls from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), two ongoing prospective cohort studies with the identical metabolomics profiling platform, gut microbiome data and objectively measured diet and lifestyle factors. The inclusion of both Hispanic and non-Hispanic cohorts may offer unique insights into the role of diet/lifestyle, gut microbiota, and metabolic pathways in the development of T2D. The findings may have great potential to identify novel targets for T2D prevention and intervention.