# The Microbiome and Bone Strength

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $640,042

## Abstract

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.; and 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.

## Key facts

- **NIH application ID:** 10854518
- **Project number:** 7R01AG067997-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Christopher John Hernandez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $640,042
- **Award type:** 7
- **Project period:** 2021-05-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854518

## Citation

> US National Institutes of Health, RePORTER application 10854518, The Microbiome and Bone Strength (7R01AG067997-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10854518. Licensed CC0.

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