The Gut Microbiome and Bone Microarchitecture

肠道微生物组和骨骼微结构

• 批准号: 9755357
• 负责人: DOUGLAS P. KIEL
• 金额: $ 60.18万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755357
• 关键词: 16S ribosomal RNA sequencing; Address; Age-Related Bone Loss; Animal Model; Animals; Architecture; Bone Density; Bone remodeling; Chronic; Cohort Studies; Collaborations; Cues; DNA; Data; Diabetes Mellitus; Diet; Dietary Assessment; Dietary Practices; Disease; Equilibrium; FDA approved; Feces; Food; Frequencies; Generations; Genes; Genetic Polymorphism; Genomics; Germ-Free; Goals; Growth; Health; Human; Immunologic Markers; Individual; Inflammation; Interferon Type II; Interleukin-17; Interleukin-4; Intervention; Intervention Studies; Lead; Length; Link; Measures; Mediating; Metabolic; Metabolism; Metagenomics; Molecular Computations; Morbidity - disease rate; Mus; Obesity; Osteogenesis; Osteoporosis; Participant; Pathway interactions; Pattern; Peripheral; Pharmaceutical Preparations; Phenotype; Physiology; Play; Population Study; Premature Mortality; Probiotics; Public Health; Questionnaires; Reporting; Research; Resolution; Ribosomal RNA; Rodent Model; Role; Sampling Studies; Scanning; Scientist; Serum; Shotgun Sequencing; Shotguns; Skeleton; Structure; Surveys; TNF gene; TNFSF11 gene; Taxonomy; Technology; Testing; Thick; Toxic effect; Translating; Woman; X-Ray Computed Tomography; aging population; analytical tool; base; bone; bone imaging; bone loss; bone metabolism; cohort; cytokine; density; experience; functional genomics; gut microbes; gut microbiome; gut microbiota; imaging modality; improved; inflammatory marker; innovation; lifestyle data; men; metagenome; microbial; microbial community; microbiome; microbiome components; mouse model; osteoporosis with pathological fracture; population based; rRNA Genes; side effect; skeletal; stool sample; therapy design

Emerging evidence suggests that gut microbes are pivotal in integrating environmental cues with host physiology and metabolism to influence many chronic conditions, including bone metabolism. This project will extend the provocative findings in animals that the gut microbiome influences the skeleton by conducting a study in humans to test the central hypothesis that the gut microbiome is associated with BMD, microarchitecture and strength. This project is a collaboration between the Framingham Osteoporosis Study and the Osteoporotic Fractures in Men Study (MrOS) that have gut microbiome specimens, high resolution peripheral quantitative computed tomography (HR-pQCT) scans, and essential dietary and lifestyle data to pursue three specific aims that are based on newly generated preliminary data showing an association between gut bacterial taxa and bone microarchitecture. Aim 1 will determine the association between 16S rRNA taxonomic profiles of the gut microbiome and five measures of bone density, architecture and strength measured using HR-pQCT. The study sample (n=3,793) is derived from the Framingham 3rd Generation and Omni Cohorts, and the MrOS Cohort. In aim 2, 864 study participants from the cohorts at the extremes of HR-pQCT derived bone measures, will have whole metagenomic shotgun sequencing performed to refine the associations observed between bone microarchitecture measures, diet, and microbiome taxonomies, and to interrogate the microbiome metabolic potential in relation to bone metabolism using newly developed analytic tools. Finally, in Aim 3, we will measure markers of inflammation, and associate them with microbiome data and BMD, bone microarchitecture and strength to assess whether they are mediating the association between the microbiome and bone. The project is significant because it focuses on osteoporosis, a disease of major public health importance that could benefit from an understanding of the potential effects of the gut microbiome on skeletal health, similar to what has been found for obesity and diabetes. This will be the first large population-based study to use state-of-the-art 16S taxonomic profiling of the gut microbiome and relate this to the most sensitive imaging modality for the human skeleton by a highly qualified team of scientists. The use of whole metagenomic shotgun sequencing in a subset of subjects from the two cohorts is an innovative way to refine the associations observed between bone microarchitecture measures and taxonomies, and to interrogate the microbiome metabolic potential and diet in relation to bone metabolism along with the accompanying inflammatory markers. Overall, the results of this study will provide the best available data on the effects of the gut microbiome on the skeleton, which could lead to interventions targeting the microbiome as a way of improving skeletal health.

新的证据表明肠道微生物在环境因素与宿主整合方面发挥着关键作用 生理和代谢影响许多慢性疾病，包括骨代谢。这个项目 将在动物身上扩展这一令人兴奋的发现，即肠道微生物组通过传导来影响骨骼 一项针对人类的研究，旨在检验肠道微生物组与 BMD 相关的中心假设， 微结构和强度。该项目是弗雷明汉骨质疏松症研究中心之间的合作 以及男性骨质疏松性骨折研究 (MrOS)，该研究拥有肠道微生物组样本，高分辨率 外周定量计算机断层扫描 (HR-pQCT) 扫描以及基本饮食和生活方式数据 追求基于新生成的显示关联的初步数据的三个具体目标 肠道细菌分类群和骨微结构之间的关系。目标 1 将确定 16S 之间的关联 肠道微生物组的 rRNA 分类学特征以及骨密度、结构和强度的五种测量方法 使用 HR-pQCT 进行测量。研究样本 (n=3,793) 来自 Framingham 第三代， Omni 队列和 MrOS 队列。在目标 2 中，来自极端情况队列的 864 名研究参与者 HR-pQCT 衍生的骨骼测量，将进行整个宏基因组鸟枪测序以完善 观察到的骨微结构测量、饮食和微生物组分类之间的关联， 并利用新开发的方法来探究与骨代谢相关的微生物组代谢潜力 分析工具。最后，在目标 3 中，我们将测量炎症标志物，并将它们与 微生物组数据和 BMD、骨微结构和强度，以评估它们是否介导 微生物组与骨骼之间的关联。该项目意义重大，因为它重点关注骨质疏松症， 一种具有重大公共卫生重要性的疾病，了解其潜在影响可能会受益 肠道微生物组对骨骼健康的影响，类似于肥胖和糖尿病的影响。这将是 第一项基于人群的大型研究，使用最先进的肠道微生物组 16S 分类学分析 并将其与高素质团队对人体骨骼最敏感的成像方式联系起来 科学家。在两个队列的一部分受试者中使用整个宏基因组鸟枪测序 是一种创新方法，可以细化观察到的骨微结构测量与骨微结构测量之间的关联 分类学，并询问微生物组代谢潜力和饮食与骨代谢的关系 以及伴随的炎症标记物。总体而言，本研究的结果将提供最好的 关于肠道微生物组对骨骼影响的现有数据，这可能会导致干预措施 针对微生物组作为改善骨骼健康的一种方式。