Targeting the Gut Microbiome to Treat Post-Traumatic Osteoarthritis

Osteoarthritis (OA) is a debilitating condition with no disease modifying treatments. We have proposed that the gut microbiome may play a role in its development and progression, and thus may represent a target for treatment. The establishment of a disease modifying treatment of OA has immense ramifications, including improved quality of life, lowered economic burden of treatment, and increased productivity of patients with OA. The purpose of this project is to study the pathogenic role of the microbiome in the development of OA as well as to develop microbiome-targeting treatments of the disease. Fecal microbiota transplants (FMTs) will be used to examine the causal relationship between microbiome dysbiosis that may develop in veterans diagnosed with post-traumatic osteoarthritis (PTOA) and belonging to the Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE). Recruitment of the Veterans into the study is completed, setting up analysis of their fecal samples using high dimensional approaches (underway at the time of this report) and FMTs in early 2024. Treatment of PTOA with microbiome pre and probiotics has been ongoing, and we find the dietary supplement hydrolyzed hylaline cartilage (hHC) to have protective effects on cartilage degeneration in a mouse model of PTOA. Progress on all these fronts is significant, with 3 manuscripts that are submitted or about to be submitted for peer review. Despite substantial institutional shutdowns caused by the COVID-19 pandemic, we are now moving ahead quickly, anticipating completion of all proposed aims by September of 2024.