The Gut Microbiome and Bone Microarchitecture

新出现的证据表明，肠道微生物在整合环境线索和宿主方面起着关键作用 生理和新陈代谢影响许多慢性疾病，包括骨代谢。这个项目 将在动物身上推广这一具有挑衅性的发现，即肠道微生物群通过引导 一项在人类身上进行的研究，旨在检验肠道微生物群与骨密度相关的中心假设， 微架构和实力。该项目是弗雷明翰骨质疏松症研究中心 和男性骨质疏松性骨折研究(MROS)，具有肠道微生物组标本，高分辨率 外周定量计算机断层扫描(HR-pQCT)，以及基本的饮食和生活方式数据 追求基于新生成的初步数据显示的关联的三个具体目标 肠道细菌分类群和骨骼微结构之间的关系。目标1将确定16之间的关联 肠道微生物组的rRNA分类图谱和骨密度、结构和强度的五项指标 用HR-pQCT测量。研究样本(n=3,793)来自Framingham第三代和 OMNI队列和MRO队列。在Aim中，2864名研究参与者来自极端情况下的队列 HR-pQCT衍生的骨骼测量，将执行整个元基因组鸟枪测序以完善 观察到的骨骼微结构措施、饮食和微生物组分类之间的关联， 并使用新开发的技术来询问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 微生物组数据和骨密度、骨微结构和强度来评估它们是否在调节 微生物群与骨骼之间的联系。这个项目意义重大，因为它专注于骨质疏松症， 一种对公共卫生具有重大意义的疾病，了解其潜在影响可能会使其受益 肠道微生物群对骨骼健康的影响，类似于对肥胖症和糖尿病的研究。这将是 第一个使用最先进的肠道微生物组16S分类图谱的大型群体研究 并将其与一个高度合格的团队对人类骨骼进行的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完整的元基因组鸟枪测序 是一种创新的方法，可以细化观察到的骨骼微结构测量和 分类，并询问与骨代谢有关的微生物组代谢潜力和饮食 以及伴随的炎症标志物。总的来说，这项研究的结果将提供最好的 关于肠道微生物群对骨骼的影响的现有数据，这可能导致干预 以微生物群为目标，作为改善骨骼健康的一种方式。

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.