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

项目摘要/摘要 人体肠道微生物区系具有巨大的催化能力和功能潜力，可作为一种内分泌 器官“，并对新陈代谢健康作出重大贡献。事实上，基础微生物学研究和培养- 以人体为基础的研究阐明了人类肠道微生物区系可能调节的多种途径 患代谢性疾病的风险，如2型糖尿病(T2D)。现有的人体研究也 显示了有希望的证据支持微生物组和流行的糖尿病之间的联系，尽管很少 已经进行了纵向研究，以建立微生物组和细菌之间的预期关系 发生T2D的风险。这项提议代表着重大的研究努力，以显著加快 从肠道之间的前瞻性关系看微生物组与T2D风险研究进展 在候选途径和T2D中运行的微生物组成、功能潜力和粪便代谢组 风险。我们还将使用网络分析和其他先进方法来询问总体元基因组学， 粪便样本中的转录组和代谢组谱用于鉴定新的微生物特征 (即微生物、其功能潜力、基因转录水平和微生物区系代谢物)和途径 这可能与T2D的发展有关。作为次要目标，我们将评估 饮食和微生物群对粪便代谢组和T2D风险的影响。此外，这些相辅相成、相互联系 研究目标将由一支经验丰富的研究团队实现，该团队由具有以下专业知识的研究人员组成 微生物组、代谢组学、生物标记物研究、糖尿病流行病学、生物统计学和生物信息学。至 为了提高研究结果的概括性和内部有效性，我们将审查这些小说 具有互补种族和社会经济特征的两个美国队列中的相关性：护士健康研究2 和拉美裔社区健康研究/拉美裔研究。这两个群体的丰富资源，包括粪便 样本，对饮食、生活方式、病史和药物使用的重复评估，纵向跟踪- 了解糖尿病状况，以及样本准备/存储和计算的基础设施，将使 调查人员以具有成本效益的方式实现拟议的目标。加强机构间协作 并确保拟议研究的成功实施，哈佛大学陈天海学院孙琦博士 和齐齐斌(在阿尔伯特·爱因斯坦医学院)将共同承担 通过多重PI机制监督整个研究的进行。总而言之，这个项目将 阐明肠道微生物组和粪便代谢组与T2D风险和便利性的前瞻性关联 与T2D风险相关的新微生物特征的发现。因此，拟议的研究具有很大的 有可能确定与微生物区系有关的新风险或有益因素，以开发更有针对性和 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.