The gut microbiome's role in the development and progression of post-traumatic osteoarthritis: A systematic review

Gut microbiome dysbiosis is linked to osteoarthritis (OA), but its specific association with post-traumatic osteoarthritis (PTOA) is less understood. This systematic review synthesizes evidence linking PTOA and the gut microbiome to clarify its role in PTOA pathogenesis.

Literature searches were conducted in PubMed, Embase, SPORTDiscus, and Web of Science through October 2025. Quantitative, original human and animal studies examining associations between the presence/severity of PTOA and gut microbiota composition and diversity were included. These measures were extracted and synthesized. Risk of bias was assessed using ROBINS-I for non-randomized and RoB 2 for randomized studies (PROSPERO registration: CRD42024496152).

Thirteen studies met inclusion criteria, all utilizing small animal PTOA models. Generally, they found significant gut microbiome differences between PTOA and control groups. Collectively, these preclinical studies provided evidence that the gut microbiome can influence biological processes underlying PTOA, particularly via inflammatory and metabolic pathways, and vice versa. Two studies examined exercise, showing it can reduce PTOA severity by slowing articular cartilage degeneration and subchondral bone loss, increase microbiome diversity, and mitigate negative effects of poor diet.

Current literature from animal models suggests the gut microbiome may play a role in PTOA development and progression, emphasizing a bidirectional "gut-joint axis." Traumatic joint injuries may lead to systemic inflammation affecting the gut microbiome, which may exacerbate joint inflammation and PTOA progression. Significant gaps remain, particularly the lack of human studies. Future research should prioritize clinically relevant animal models and human studies to elucidate the gut microbiome's role in PTOA pathogenesis.