# The contribution of the intestinal microbiota to fracture-induced pain

> **NIH VA IK1** · PHOENIX VA HEALTH CARE SYSTEM · 2024 · —

## Abstract

Bone fractures are painful injuries that disproportionally affect Veterans. Emerging evidence suggests that the
intestinal microbiota is a significant regulator of inflammatory, neuropathic, and visceral pain through production
of neuroactive metabolites and inflammatory mediators. However, the contribution of the gut microbiome to pain
following traumatic bone injuries has remained unexplored. Therefore, the overall goal of this proposal is to
establish the gut microbiota as a therapeutic target to modulate the inflammatory pain response to and
throughout fracture healing. Our central hypothesis posits that the intestinal microbiota is a critical regulator of
pain following fracture through inflammatory signals and production of neuroactive metabolites, and that dietary
supplementation with probiotics will alleviate pain during fracture healing. We first propose to assess post-
fracture pain and function in mice with a depleted microbiome achieved through a broad-spectrum antibiotic
cocktail, and whether dietary supplementation with probiotics will improve these outcomes (Aim 1). The
indigenous microbiota and probiotics produce a variety of neuroactive metabolites that influence host metabolism
and may contribute to pain sensitization and desensitization during bone healing. We will characterize the role
of the intestinal microbiota in metabolic flexibility after fractures using serum metabolomics and metabolic
phenotyping studies (Aim 2). Together the proposed experiments will determine whether the gut microbiota is a
valid therapeutic target for managing pain during recovery from fractures.
The candidate’s long-term career goal is to become an independent VA investigator with a research focus on
identifying nutrition-based approaches to improve patient outcomes and quality of life while also enhancing
healing of orthopaedic injuries. The award of a CDA-1 will enable the PI to leverage his cumulative expertise and
gain new skills in the assessment of pain, function, as well as cell and tissue metabolism to develop novel, yet
easily implemented approaches aimed at improving the quality of life of Veterans suffering from painful
musculoskeletal injuries and ailments. The proposed work will be completed using a comprehensive training
plan under the guidance of an experienced, multidisciplinary mentoring team consisting of VA investigators. This
will include recurring meetings with the mentoring team and hands-on training in metabolomics and behavioral
assessments of pain and function. The planned innovative research will advance the understanding of the
interconnectedness between the gut microbiota, pain, and metabolism following common traumatic bone injuries
experienced by Veterans. This may lead to new treatments that decrease the reliance on harmful pain-relieving
pharmacological drugs throughout the post-fracture recovery period. This CDA-1 project complements his prior
dissertation work that focused on the inflammatory and gut microbiota inf...

## Key facts

- **NIH application ID:** 10534888
- **Project number:** 1IK1RX003783-01A2
- **Recipient organization:** PHOENIX VA HEALTH CARE SYSTEM
- **Principal Investigator:** Joseph Lewis Roberts
- **Activity code:** IK1 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-11-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534888

## Citation

> US National Institutes of Health, RePORTER application 10534888, The contribution of the intestinal microbiota to fracture-induced pain (1IK1RX003783-01A2). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10534888. Licensed CC0.

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