Metabolomics signatures underlying diet, lifestyle and gut microbiota for diabetes

总结/摘要 血液代谢组学分析可以检测到代谢的细微变化，这可能预示着后者 2型糖尿病（T2 D）的发展。这既可以揭示T2 D途径的早期步骤，也可以 提供了一种新工具来识别高风险个体。西班牙裔/拉美裔，美国最大且增长最快的 少数民族人群的糖尿病患病率比非西班牙裔白人高66%。美国 西班牙裔/拉丁美洲人在生物学和社会文化特征上是多样的，因此可能具有不同的饮食， 生活方式和肠道菌群模式可能影响与T2 D有关的代谢物。本课程的主要目的 该项目旨在确定T2 D风险的代谢组学特征，并研究饮食、生活方式和肠道菌群 影响与T2 D相关的代谢组学特征。特别是，我们建议执行高吞吐量 来自1000对T2 D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）中的事件病例和匹配对照，以确定 与美国西班牙裔/拉美裔T2 D发病相关的新代谢组学特征。在SOL中，我们将 利用现有的大量实验室指标数据（例如空腹血糖和胰岛素、HbA 1c和2小时血糖 口服后葡萄糖耐量试验）和客观测量的行为（例如，生物标志物加速度测量 测量的饮食因素）。利用正在进行的肠道微生物组数据 在SOL项目中，我们将描述肠道微生物组成和功能特征， 与T2 D相关的血浆代谢组学特征，并检查饮食在调节肠道菌群中的作用- 相关代谢物。将在非西班牙裔队列中进一步检查与T2 D相关的代谢组学特征 纳入了来自护士健康研究（NHS）的1，500对T2 D事件病例和匹配对照，以及 医疗保健专业人士随访研究（HPFS），两项正在进行的前瞻性队列研究， 代谢组学分析平台、肠道微生物组数据和客观测量的饮食和生活方式因素。的 纳入西班牙裔和非西班牙裔人群可能会对饮食/生活方式、消化道和胰岛素抵抗的作用提供独特的见解。 微生物群和代谢途径在T2 D的发展。这些发现可能对 识别2型糖尿病预防和干预的新靶点。

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.