Human Gut Microbiome and Incident Diabetes Risk in U.S. Populations

项目总结/摘要 人类肠道微生物群具有巨大的催化能力和功能潜力，可以作为“内分泌”， 器官”，并显着有助于代谢健康。实际上，基础微生物研究和培养- 基于人类的研究已经阐明了人类肠道微生物群可以调节的多种途径 患代谢性疾病的风险，如2型糖尿病（T2 D）。现有的人体研究还 显示出有希望的证据支持微生物组与流行糖尿病之间的联系，尽管很少 已经进行了纵向研究，以建立微生物组与 发展T2 D的风险。这项提案代表了重大的研究努力，以显着加快 通过检查肠道之间的前瞻性关系，在微生物组和T2 D风险的研究中取得进展 微生物组成，功能潜力和粪便代谢组，在候选途径和T2 D中运行 风险我们还将使用网络分析和其他先进的方法来询问整体宏基因组， 粪便样品中的元转录组学和代谢组学谱，用于鉴定新的微生物特征 (i.e.,微生物，它们的功能潜力，基因转录水平和微生物群代谢物）和途径 可能与T2 D的发展有关。作为第二个目标，我们将评估 饮食和微生物组对粪便代谢组和T2 D风险的影响。此外，这些相互补充、相互联系的 研究目标将由一个经验丰富的研究者团队实现，该团队由具有以下专业知识的研究人员组成： 微生物组学、代谢组学、生物标志物研究、糖尿病流行病学、生物统计学和生物信息学。到 为了更好地推广和研究结果的内部效度，我们将研究这些新的 美国两个具有互补种族和社会经济特征的队列研究中的相关性：护士健康研究II 西班牙裔社区健康研究/拉丁裔研究。这两个群体的丰富资源，包括粪便 样本，饮食，生活方式，病史和药物使用的重复评估，纵向随访- 糖尿病状态，以及用于样品制备/存储和计算的基础设施，将使 调查人员以成本效益高的方式实现拟议目标。加强机构间合作 孙琦博士（哈佛T. H.）阐教 公共卫生）和齐启斌（阿尔伯特爱因斯坦医学院）将共同负责 通过多重PI机制监督研究的整体进行。总之，该项目将 阐明肠道微生物组和粪便代谢组与T2 D风险的前瞻性关联， 发现与T2 D风险相关的新微生物特征。因此，这项研究具有很大的意义。 有可能确定新的微生物群相关的风险或有益因素， 预防和管理糖尿病的个体化策略。

Project Summary/Abstract Human gut microbiota, with its massive catalytical capacity and functional potential, may act as an “endocrine organ” and significantly contribute to metabolic health. Indeed, basic microbiological research and culture- based human studies have elucidated multiple pathways through which human gut microbiota may modulate the risk of developing metabolic diseases, such as type 2 diabetes (T2D). Existing human studies also demonstrated promising evidence supporting a link between microbiome and prevalent diabetes, although few longitudinal studies have been conducted to establish a prospective relationship between microbiome and the risk of developing T2D. This proposal represents major research efforts to significantly accelerate the advances in the research of microbiome and T2D risk by examining prospective relationships between gut microbial composition, functional potential, and fecal metabolome that operate in candidate pathways and T2D risk. We will also use network analysis and other advanced methods to interrogate the overall metagenomic, metatranscriptomic, and metabolomic profiles in fecal samples for the identification of novel microbial features (i.e., microbes, their functional potential, gene transcription levels, and microbiota metabolites) and pathways that might be involved in the development of T2D. As a secondary aim, we will evaluate the interplay between diet and microbiome on fecal metabolome and T2D risk. Furthermore, these complementary, inter-connected study aims will be realized by an experienced investigator team consisting of researchers with expertise in microbiome, metabolomics, biomarker research, diabetes epidemiology, biostatistics, and bioinformatics. To facilitate better generalizability and internal validity of research findings, we will examine these novel associations in two US cohorts with complementary ethnic and socioeconomic profiles: Nurses’ Health Study II and Hispanic Community Health Study / Study of Latinos. Rich resources of these two cohorts, including fecal samples, repeated assessments of diet, lifestyle, medical history, and use of medications, longitudinal follow- up on diabetes status, and infrastructure for sample preparation/storage and computing, will empower the investigators to accomplish the proposed aims cost-effectively. To strengthen between-institution collaboration and ensure a successful implementation of the proposed research, Drs. Qi Sun (at Harvard T.H. Chan School of Public Health) and Qibin Qi (at Albert Einstein College of Medicine) will share the responsibility of overseeing the overall conduct of research through the Multiple PI mechanism. In summary, this project will elucidate prospective associations of gut microbiome and fecal metabolome with T2D risk and facilitate discoveries of novel microbial features relevant to T2D risk. As such, the proposed research has a great potential to identify novel microbiota-related risk or beneficial factors for developing more targeted and individualized strategies for the prevention and management of diabetes.