Alterations in Gut Microbiota and Post-Traumatic Osteoarthritis
Abstract
Osteoarthritis is a disease involving degradation of the cartilage in joints. Degradation of cartilage characteristic of osteoarthritis results in pain during joint movement and can progress to the point where patients cannot perform activities of daily living. While there are methods of reducing joint pain, there are no methods to reverse the structural changes in osteoarthritis, and the only intervention shown to completely remove joint pain and restore joint function is total joint replacement (an artificial hip, knee, etc.). Mechanical loading is a major contributor to the development of osteoarthritis. Osteoarthritis resulting from an isolated mechanical overload or trauma is referred to as post-traumatic osteoarthritis. A condition known as low-grade chronic systemic inflammation has been identified as a non-mechanical contributor to the development of osteoarthritis. Low-grade chronic systemic inflammation is a condition in which there are mild, chronic increases in immune system activity throughout the body. Low-grade chronic systemic inflammation is often observed in obesity and type 2 diabetes, two of the primary risk factors for the development of osteoarthritis. However, low-grade chronic systemic inflammation also occurs in people without obesity and can be caused by alterations in the gut microbiome. Central Critical Problem: The proposed work tests the idea that alterations in gut microbiota that cause low-grade chronic systemic inflammation enhances cartilage degeneration in the weeks following an isolated overloading event. If our hypothesis is correct, it would suggest that individuals with altered microbiota causing low-grade chronic systemic inflammation are more likely to develop osteoarthritis because cartilage degeneration occurs faster than reparative processes. To test the concept in a controlled manner, we will apply mechanical loads to the knee joints of mice with and without microbiome-induced low-grade chronic systemic inflammation and determine if there are differences in the subsequent rate of cartilage degeneration. Innovation of the Idea: The proposed work is innovative in that it uses an animal model in which the alterations in the microbiome. The mouse strain (TLR5KO mice) used in the study addresses a major roadblock for understanding non-mechanical contributors to osteoarthritis because low-grade chronic systemic inflammation is derived from the microbiome. Additionally, the work has the potential to provide information about the separate effects of obesity and low-grade chronic systemic inflammation on osteoarthritis. Ultimate Applicability and Impact of the Research: Understanding non-mechanical contributors to post-traumatic osteoarthritis is potentially impactful because non-mechanical contributors can possibly be addressed with pro- and prebiotics and changes in diet, while reducing mechanical loading is not possible in active duty military populations. The proposed work may indicate that simple alterations of gut flora (including pre- and probiotics in the diet) or changing diet have the potential to reduce the risk of developing osteoarthritis after excessive loading (e.g., a fall or short period of heavy exercise). Changes in diet and the application of pre- and probiotics is inexpensive and relatively easy to apply to active duty military populations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510239
Entities
People
- Christopher Hernandez
Organizations
- Cornell University
- United States Army