# Role of the Gut Microbiome in Implant Loosening

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2020 · $172,700

## Abstract

The main cause of total joint replacement failure is aseptic loosening due to particle-induced peri-implant
osteolysis. The annual cost of failure is more than $10B/year in the U.S. and by 2030 more than 350,000
patients per year will need revision surgery. The current thinking is that peri-implant osteolysis is caused by
particle-induced inflammation, leading to release of osteoclast-stimulating cytokines. We propose to begin
testing the novel hypothesis that there is bi-directional cross-talk between the gut microbiome and the implant
microenvironment that is integral to the progression of particle-induced osteolysis. The gut microbiome is the
collective genetic material of the bacteria, fungi and viruses in the intestinal track. Gut ecology can be altered
by diet, drugs, environment, host genetics and early-life microbial exposure. The symbiotic relationship
between gut microorganisms and the host is essential to overall health. The scientific premise for the project is
the growing recognition that manipulating the gut microbiome affects musculoskeletal tissues and our new data
that the gut microbiome is altered in a rat model of particle-induced peri-implant osteolysis and that aseptic
loosening is accelerated in total hip replacement patients who have irritable bowel disease. Given these
observations we believe there is sufficient evidence to study the possibility of cross-talk between the digestive
and musculoskeletal systems, which could lead to a vicious cycle whereby an initial inflammatory response in
the musculoskeletal system contributes to gut dysbiosis, which, in turn, exacerbates the musculoskeletal
inflammatory process. We propose testing the hypothesis through two specific aims: (1) Determining if altering
the gut microbiome through use of a prebiotic dietary supplement affects the progression of particle-induced
peri-implant osteolysis in our rat model and (2) Characterizing how particle-induced peri-implant osteolysis
alters the gut microbiome. If this new hypothesis is correct, then there are two novel therapeutic opportunities
for preventing or treating peri-implant osteolysis: (1) using dietary supplements to alter the gut microbiome,
thus altering the gut-joint feedback loop and (2) interfering with the joint-gut feedback loop. Mechanisms of
action for manipulation of the gut microbiome profile to affect remote site tissues include mucosal-mediated
immunity, nutrition or release of bacterial products. We will investigate release of bacterial products from the
gut as a mechanism of action. How the “challenge” in the musculoskeletal system influences the gut is
currently not known and we will begin to study this. Finally, it is also possible that there is a gut bacterial profile
unique to particle-induced osteolysis, which would provide a potential novel biomarker for this condition.

## Key facts

- **NIH application ID:** 9883720
- **Project number:** 5R21AR075130-02
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** D Rick Sumner
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,700
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883720

## Citation

> US National Institutes of Health, RePORTER application 9883720, Role of the Gut Microbiome in Implant Loosening (5R21AR075130-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883720. Licensed CC0.

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