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

人类肠道微生物组和美国人群的糖尿病风险

• 批准号: 10094713
• 负责人: Qibin Qi
• 金额: $ 66.96万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-19 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10094713
• 关键词: Acids; Adult; Age; Animal Experiments; Animal Feed; Animals; Bacteria; Bile Acids; Bioinformatics; Biological; Biological Markers; Biometry; Branched-Chain Amino Acids; Butyrates; Choline; Classification; Clinical; Coffee; Collaborations; Cross-Sectional Studies; Data; Demographic Factors; Development; Diabetes Mellitus; Diabetes prevention; Diet; Dietary Fiber; Effectiveness of Interventions; Endocrine Glands; Ensure; Enzymes; Epidemiology; Ethnic Origin; Etiology; Gender; Gene Expression; Gene Family; Genetic Transcription; Health; Healthcare; Hispanic Community Health Study/Study of Latinos; Human; Incidence; Inflammation; Infrastructure; Institution; Intake; Intervention; Levocarnitine; Life Style; Link; Longitudinal Studies; Measures; Meat; Medical History; Medicine; Metabolic; Metabolic Diseases; Metabolism; Metagenomics; Methods; Microbe; Microbiology; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Pathway Analysis; Pathway interactions; Pattern; Pharmaceutical Preparations; Physical activity; Physiological Processes; Plants; Play; Population; Preparation; Prevalence; Prevention; Prevention strategy; Process; Prospective Studies; Public Health Schools; Qi; Research; Research Design; Research Personnel; Resources; Risk; Role; Sample Size; Sampling; Study of Latinos; Supervision; Taxonomy; The Sun; Weight maintenance regimen; Woman; base; case control; cohort; college; cost; diabetes management; diabetes risk; dietary; energy balance; enzyme pathway; experience; fecal metabolome; follow-up; frontier; fruits and vegetables; glucose metabolism; gut microbiome; gut microbiota; high risk; improved; individual variation; individualized prevention; men; metabolomics; metatranscriptomics; microbial; microbiome; microbiome research; microbiota; microbiota metabolites; multiple omics; mutualism; new technology; novel; personalized approach; personalized strategies; polyphenol; preventive intervention; prospective; socioeconomics; trimethyloxamine

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.

项目概要/摘要 人类肠道微生物群具有巨大的催化能力和功能潜力，可能充当“内分泌系统” 器官”并对代谢健康做出了重大贡献。事实上，基础微生物研究和培养- 基于人类的研究阐明了人类肠道微生物群可能调节的多种途径 患代谢疾病的风险，例如 2 型糖尿病 (T2D)。现有的人类研究也 证明了有希望的证据支持微生物组与流行的糖尿病之间的联系，尽管很少有证据 已经进行了纵向研究，以建立微生物组与环境之间的前瞻性关系。 发生 T2D 的风险。该提案代表了显着加速的重大研究工作 通过检查肠道之间的前瞻性关系，微生物组和 T2D 风险研究取得进展 在候选途径和 T2D 中发挥作用的微生物组成、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整体宏基因组， 粪便样本中的宏转录组学和代谢组学特征，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，我们将评估之间的相互作用 饮食和微生物组对粪便代谢组和 T2D 风险的影响。此外，这些互补的、相互关联的 研究目标将由经验丰富的研究团队来实现，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、生物标志物研究、糖尿病流行病学、生物统计学和生物信息学。到 促进研究结果更好的普遍性和内部有效性，我们将研究这些新颖的 两个具有互补种族和社会经济状况的美国队列的关联：护士健康研究 II 和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 了解糖尿病状况以及样本制备/存储和计算的基础设施，将赋予 调查人员以具有成本效益的方式实现拟议目标。加强机构间合作 并确保拟议研究的成功实施，博士。孙琪（哈佛大学陈曾熙学院） 公共卫生学院）和齐其斌（阿尔伯特·爱因斯坦医学院）将共同承担以下责任： 通过多重 PI 机制监督研究的整体进行。综上所述，本项目将 阐明肠道微生物组和粪便代谢组与 T2D 风险的前瞻性关联，并促进 与 T2D 风险相关的新微生物特征的发现。因此，所提出的研究具有很大的意义 识别新的微生物群相关风险或有益因素的潜力，以开发更有针对性和 预防和管理糖尿病的个体化策略。