# The Gut Microbiome and Bone Microarchitecture

> **NIH NIH R01** · HEBREW REHABILITATION CENTER FOR AGED · 2021 · $581,835

## Abstract

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.

## Key facts

- **NIH application ID:** 10208709
- **Project number:** 5R01AR061445-09
- **Recipient organization:** HEBREW REHABILITATION CENTER FOR AGED
- **Principal Investigator:** DOUGLAS P. KIEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $581,835
- **Award type:** 5
- **Project period:** 2012-05-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208709

## Citation

> US National Institutes of Health, RePORTER application 10208709, The Gut Microbiome and Bone Microarchitecture (5R01AR061445-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10208709. Licensed CC0.

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