The Gut Microbiome and Bone Microarchitecture

肠道微生物组和骨骼微结构

• 批准号: 10208709
• 负责人: DOUGLAS P. KIEL
• 金额: $ 58.18万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10208709
• 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; dietary; 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.

新出现的证据表明，肠道微生物在整合环境线索与宿主方面至关重要。 生理学和代谢影响许多慢性疾病，包括骨代谢。这个项目 将扩展动物的挑衅性发现，即肠道微生物组通过传导影响骨骼， 一项在人类中进行的研究，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。这个项目是一个合作， 以及男性骨质疏松性骨折研究（MrOS），该研究具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，以及必要的饮食和生活方式数据， 追求三个具体目标，这些目标基于新生成的初步数据，显示出一种关联 肠道细菌分类群和骨骼微结构之间的联系。目标1将确定16 S之间的关联 肠道微生物组的rRNA分类谱和骨密度、结构和强度的五项指标 使用HR-pQCT测量。研究样本（n= 3，793）来自第三代Fractionary， Omni队列和MrOS队列。在目标2中，864名来自极端人群的研究参与者， HR-pQCT衍生的骨测量，将进行全宏基因组鸟枪测序以细化 观察到骨微结构测量、饮食和微生物组分类之间的关联， 并使用新开发的微生物群代谢潜力来询问与骨代谢相关的微生物群代谢潜力， 分析工具。最后，在目标3中，我们将测量炎症标志物，并将其与 微生物组数据和BMD，骨微结构和强度，以评估它们是否介导了骨密度的变化。 微生物组与骨骼之间的联系。该项目意义重大，因为它侧重于骨质疏松症， 一种具有重大公共卫生意义的疾病，可以从了解其潜在影响中获益 肠道微生物组对骨骼健康的影响，类似于肥胖和糖尿病的发现。这将是 这是第一项使用最先进的16 S肠道微生物组分类学分析的大型人群研究 并将其与人体骨骼最敏感的成像模式相关联， 科学家在来自两个队列的受试者子集中使用全宏基因组鸟枪测序 是一种创新的方法，以改善骨微结构测量之间观察到的关联， 分类，并询问与骨代谢相关的微生物组代谢潜力和饮食 沿着炎症标记。总的来说，这项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，这可能导致干预措施 以微生物组为目标来改善骨骼健康。

项目成果

Harmonizing finite element modelling for non-invasive strength estimation by high-resolution peripheral quantitative computed tomography.

通过高分辨率外围定量计算机断层扫描协调有限元建模以进行非侵入性强度估计。

• DOI: 10.1016/j.jbiomech.2018.08.030
• 发表时间: 2018
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Whittier,DanielleE;Manske,SarahL;Kiel,DouglasP;Bouxsein,Mary;Boyd,StevenK
• 通讯作者: Boyd,StevenK

Diabetes and Deficits in Cortical Bone Density, Microarchitecture, and Bone Size: Framingham HR-pQCT Study.

糖尿病与皮质骨密度、微结构和骨大小的缺陷：Framingham HR-pQCT 研究。

• DOI: 10.1002/jbmr.3240
• 发表时间: 2018-01
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
• 作者: Samelson EJ;Demissie S;Cupples LA;Zhang X;Xu H;Liu CT;Boyd SK;McLean RR;Broe KE;Kiel DP;Bouxsein ML
• 通讯作者: Bouxsein ML

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk.

• DOI: 10.1002/jbmr.4494
• 发表时间: 2022-03
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Heritability and Genetic Correlations for Bone Microarchitecture: The Framingham Study Families.

• DOI: 10.1002/jbmr.2915
• 发表时间: 2017-01
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
• 作者: Karasik D;Demissie S;Zhou Y;Lu D;Broe KE;Bouxsein ML;Cupples LA;Kiel DP
• 通讯作者: Kiel DP