Gut microbial factors that increase bone tissue strength

增加骨组织强度的肠道微生物因素

基本信息

批准号：
10707012
负责人：
Erika Leah Cyphert
金额：
$ 6.95万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707012
关键词：
16S ribosomal RNA sequencing Activities of Daily Living Address Adult Age Age Months Aging Animals Antibiotics Bacteria Biocompatible Materials Biological Bone Density Bone Matrix Bone Tissue Chronic Elderly Exhibits Exposure to Fracture Funding Genes Goals Grant Health Care Costs Healthcare Systems Human Impairment Individual Intervention Knock-out Knowledge Lead Life Link Measures Metagenomics Methods Microbe Modification Morbidity - disease rate Mus Musculoskeletal Diseases Orthopedics Osteoporosis Osteoporosis prevention Outcome Property Public Health Research Research Personnel Research Proposals Research Training Risk Science Shotguns Source System Taxonomy Therapeutic Training Training Activity United States Work Writing age related aged biomaterial development bone bone quality bone strength career fragility fracture gut bacteria gut microbes gut microbiome gut microbiota improved in vivo in vivo Model male metagenomic sequencing microbial microbiome microbiota mortality osteoporosis with pathological fracture prevent sex

16S ribosomal RNA sequencing Activities of Daily Living Address Adult Age Age Months Aging Animals Antibiotics Bacteria Biocompatible Materials Biological Bone Density Bone Matrix Bone Tissue Chronic Elderly Exhibits Exposure to Fracture Funding Genes Goals Grant Health Care Costs Healthcare Systems Human Impairment Individual Intervention Knock-out Knowledge Lead Life Link Measures Metagenomics Methods Microbe Modification Morbidity - disease rate Mus Musculoskeletal Diseases Orthopedics Osteoporosis Osteoporosis prevention Outcome Property Public Health Research Research Personnel Research Proposals Research Training Risk Science Shotguns Source System Taxonomy Therapeutic Training Training Activity United States Work Writing age related aged biomaterial development bone bone quality bone strength career fragility fracture gut bacteria gut microbes gut microbiome gut microbiota improved in vivo in vivo Model male metagenomic sequencing microbial microbiome microbiota mortality osteoporosis with pathological fracture prevent sex

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项目摘要

PROJECT SUMMARY/ABSTRACT Age-related fragility fractures impose healthcare costs exceeding $25 billion annually in the United States. Risk of fragility fracture is due to both decreased bone mineral density (bone quantity) and bone tissue quality. Current therapeutics for osteoporosis are effective at increasing bone quantity but do not directly address aspects of bone tissue quality (the contents and organization of the bone matrix). Several studies have recently discovered a link between the composition of the gut microbiome and bone strength. Previous work from the sponsor’s group has demonstrated that perturbations to the constituents of the gut microbiome can impair bone tissue material properties. A more recent, unexpected, and exciting finding demonstrated that specific alterations of the composition of the gut microbiome increased the strength of the bone matrix. Prior work generated a list of microbial taxa that had an increased abundance in animals with enhanced bone tissue strength relative to unaltered controls. Nevertheless, the specific species and functional capacity of the bacteria contributing to the increased bone strength remain to be elucidated. Additionally, prior studies manipulating the components of the gut microbiota were predominantly completed in young, male mice. Since interventions to prevent fragility fractures are most likely applied to older adults, it is critical to determine if the same alterations in the gut microbiota can influence bone tissue strength in aged animals of both sexes. This proposal addresses the following questions: what are the taxonomic and functional constituents of the microbiota responsible for increasing bone tissue strength in mice; and is it possible to increase the strength of the bone matrix by altering the gut microbiota in late adulthood? The specific aims are to 1) isolate gut microbial constituents contributing to increased bone tissue strength in young mice and 2) determine the effects of modifying the gut microbiota to increase bone tissue strength in aged mice. The overarching goal of the proposal is to isolate and characterize constituents of the gut microbiota that enhance bone tissue strength and quality in growing and aged mice. Research from this proposal builds upon prior findings from the sponsor’s group while enabling the candidate to transition to an independent investigator by gaining expertise in in vivo models and microbiome metagenomic analysis. The long-term goal of the candidate is to pursue a career developing delivery systems/biomaterials that regulate the constituents of the microbiome for applications such as musculoskeletal disorders and aging. Development of biomaterials that regulate the microbiota requires knowledge of taxonomic and metagenomic analysis of microbiota in in vivo models. Therefore, this application is to fund training in in vivo experimentation and manipulation of the gut microbiome while increasing expertise orthopaedic research. Training activities will also include exposure to team science, grant writing, and didactic coursework in the microbiome.

项目摘要/摘要在美国，与年龄有关的脆性骨折每年施加超过250亿美元的医疗费用。风险易碎性骨折是由于骨矿物质密度（骨骼数量）和骨组织质量降低所致。当前对骨质疏松症的治疗可有效增加骨骼数量，但不能直接解决骨组织质量的各个方面（骨基质的内容和组织）。最近有几项研究发现了肠道微生物组和骨骼强度的组成之间的联系。以前的工作赞助商的小组表明，对肠道微生物组的成分的扰动可能会损害骨组织材料的特性。最近，出乎意料且令人兴奋的发现证明了特定的肠道微生物组组成的改变会增加骨基质的强度。先前的工作产生了一个微生物分类群的列表，该分类群的丰度增加，骨组织增强强度相对于不变的对照。然而，特定的规格和功能能力导致骨强度增加的细菌仍有待阐明。另外，先前的研究在年轻的雄性小鼠中，操纵肠道微生物群的成分主要完成。自从预防脆弱性骨折的干预措施很可能适用于老年人，至关重要的是确定是否是否肠道微生物群的同样改变会影响男女老年动物的骨组织强度。这提案解决以下问题：分类学和功能构成是什么微生物群负责增加小鼠骨组织强度；并且有可能增加骨基质通过成年后期改变肠道菌群？具体目的是1）分离肠有助于增加小鼠骨组织强度的微生物成分，2）确定修饰肠道菌群以增加老年小鼠骨组织强度的影响。总体目标该建议是隔离并表征肠道菌群的一致性，从而增强骨组织强度以及成长和老化的小鼠的质量。该提案的研究基于先前发现赞助商的小组，同时使候选人能够通过获得专业知识过渡到独立研究者在体内模型和微生物组宏基因组分析中。候选人的长期目标是追求职业开发递送系统/生物材料，以调节微生物组的构成肌肉骨骼疾病和衰老等应用。开发调节的生物材料微生物群需要了解体内模型中微生物群的分类学和宏基因组分析。因此，此应用是为了资助体内实验和操纵肠道微生物组的培训同时提高专业知识的骨科研究。培训活动还将包括接触团队科学，授予写作，并在微生物组中进行教学课程。