Associations between gut microbiota, flagellin production and bone microstructure

描述(由申请人提供)：拟议的工作检查肠道微生物区系和骨骼之间的相互作用。早期证据表明，肠道微生物区系的组成和功能与大多数导致骨质疏松症的因素有关。这项高级研究员奖学金有两个目标：培训目标是向高级研究员提供肠道微生物组研究方面的专业知识，以及用于操纵和检查肠道微生物组的实验方法，他计划在获奖后阶段将肠道微生物组应用于骨丢失情况。研究目的是验证与Toll样受体5(TLR5)缺乏相关的肠道微生物区系改变导致骨量减少的假设。肠道的慢性炎症，如炎症性肠炎，会导致骨质丢失。由于肠道微生物区系的变化，TLR5基因缺陷小鼠表现出低水平的慢性肠道炎症，但S不知道TLR5基因缺陷小鼠是否也经历了骨骼的变化。将在TLR5缺陷小鼠的轴向和附件骨骼中检测骨量，野生型和接受TLR5缺陷小鼠肠道微生物区系移植的野生型小鼠(这一过程已知移植肠道中的慢性炎症状态)。拟议的工作将为高级研究员提供使用无菌设施的培训，包括移植肠道微生物区系和为未来的骨骼研究分析肠道菌群的组成。

DESCRIPTION (provided by applicant): The proposed work examines interactions between gut microbiota and bone. Early evidence suggests that the composition and function of the gut microbiota is correlated with most of the factors leading to the development of osteoporosis. This senior fellowship has two goals: the training goal is to provide the senior fellow with expertise in the study of the gut microbiome and experimental methods used to manipulate and examine the gut microbiome which he plans to apply to conditions of bone loss in the post-award period. The research objective is to test the hypothesis that alterations in gut microbiota associated with toll-like receptor 5 (TLR5) deficiency lead to reductions in bone mass. Chronic inflammation in the gut as seen in inflammatory bowel results in bone loss. TLR5 deficient mice display low level chronic inflammation in the gut as a result of changes in gut microbiota, but it s not known if TLR5 deficient mice also experience alterations in bone. Bone mass will be examined in the axial and appendicular skeleton of TLR5 deficient mice, wild type and in wild type mice receiving a transplant of gut microbiota from TLR5 deficient mice (a process known to transplant the state of chronic inflammation in the gut). The proposed work will provide the senior fellow with training in the use of a germ free facility, including transplantation of gut microbiota and analysis of the composition of the gut flora for future studies in bone.