R01AG067997

The microbiome and bone strength - 7. Project Summary

The microbiome has been associated with disease processes throughout the body and is therefore an intriguing target for therapeutics and diagnostics. Multiple preclinical studies have shown that the microbiome can influence bone. Our prior work has indicated that modifications to the microbiome during bone acquisition can influence bone strength by modifying bone tissue quality. "Bone quality" describes aspects of bone that are not well represented by measures of bone mineral density (BMD). Our findings raise the intriguing possibility that microbiome-based therapies may be able to improve bone tissue quality - a contributor to bone strength that is not directly targeted by existing therapies.

In the proposed work, we ask: What microbial taxa within the gut microbiota are responsible for changes in bone strength and tissue quality? What is the pathway linking the gut microbiota to bone strength and tissue quality? And how does the influence of the microbiome on bone strength vary based on age and the stage of skeletal maturity (growing v. skeletally mature)?

The proposed work is based on our preliminary studies in which we associated microbiome-induced impairment of bone strength with large changes in the microbial taxonomic and genetic composition, as well as impaired production of vitamin K by the gut microbiota and reduced abundance of matrix-bound osteocalcin (a vitamin K dependent protein).

The proposed work has three aims:
1) Determine the components of the gut microbiota that lead to impaired bone strength and quality.
2) Determine the dependence of microbiome-induced reductions in bone tissue quality on microbiome-derived vitamin K.
3) Determine the modifications in bone matrix caused by changes in the microbiome in an adult skeleton as compared to the growing skeleton.

The proposed work includes manipulation of the gut microbiota through transfer of gut flora among animals using gnotobiotic chambers and depletion of microbes ("knock out") from the gut microbiota using narrow-spectrum antibiotics. Taxonomic and functional characterization of the gut microbiota and examination of the resulting bone biomechanical, chemical, and geometrical phenotypes is performed at the whole organ, micro- and nanoscale.

By establishing a mechanistic relationship between the microbiome and bone strength in both the growing and adult skeleton, the proposed work will perform the necessary first steps toward the identification of microbiome therapeutics that modulate bone tissue quality to reduce bone fragility.

San Francisco Regents Of The University Of California

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

San Francisco, California 941432203 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 477% from $616,787 to $3,558,912.