# Influence of the gut microbiome on normal and senile fracture healing

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $230,620

## Abstract

Summary
Impaired fracture healing place considerable financial, physical, and mental burdens on individuals, especially
in the geriatric population, which renders the need for new therapies to accelerate healing of paramount
importance. With the growing evidence that the gut microbiota regulates skeletal homeostasis, we asked whether
the beneficial effects of probiotic intake on bone health may be similar or different in the case of traumatic bone
injuries. Thus, while it is widely accepted that bone mineral density only predicts fracture risk, and is not indicative
of bone healing, the effects of microbiota on bone modeling and systemic inflammation in the context of fracture
healing remains unexplored. Moreover, whether a single probiotic can positively impact senile fractures has also
not been previously reported. Therefore, the overall goal of this proposal is to establish the gut microbiota as a
modulator of the inflammatory as well as the osteogenic responses to fracture healing in the context of aging.
In our preliminary data section, we show that that dietary supplementation with the candidate probiotic
Bifidobacterium adolescentis alters the profile of serum cytokines, protects against fracture induced systemic
bone loss, increases fracture callus bone volume, and accelerates the healing sequelae. We therefore
hypothesize that the microbiome is a key regulator of secondary bone healing through the modulation of
systemic innate inflammatory signals, and that dietary supplementation with probiotics that modulate these
inflammatory signals may be used as therapeutic modalities to accelerate fracture healing.
While growing evidence points to beneficial effects of probiotics on skeletal homeostasis, their role in skeletal
repair and regeneration remains elusive. Here we propose to first compare fracture healing rates between germ-
free and conventional mice, and to determine whether this will be influenced by colonization with aged-
microbiome (Aim 1). The current dogma posits that the gut microbiota regulates bone mass through mechanisms
involving shifts in inflammatory cell populations and their respective cytokines as well as through maintenance
of the intestinal barrier. In the second Aim or this proposal, we will establish the relevance of the gut microbiota
to induce changes in the gut leakiness responsible for exacerbated inflammation observed during aging and in
the context of traumatic bone healing. Thus, we will establish the therapeutic efficacy of probiotic manipulation
of the gut microbiome for accelerated secondary bone fracture repair in aged mice (Aim 2).
Discovering specific bacterial taxa within the intestine that accelerate bone healing will be essential information
for the characterization of a eubiotic microbiome that may elicit optimal fracture repair rates. Moreover, this
information will enable the development of therapeutic approaches whereby the identification of gut microbial
obstructions to fracture healing within ...

## Key facts

- **NIH application ID:** 9875570
- **Project number:** 1R21AG065977-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Moulay Hicham DRISSI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $230,620
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875570

## Citation

> US National Institutes of Health, RePORTER application 9875570, Influence of the gut microbiome on normal and senile fracture healing (1R21AG065977-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9875570. Licensed CC0.

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