The Gut Microbiome and Knee Osteoarthritis: A Review of Emerging Pathophysiologic Links

Background Knee osteoarthritis (OA), a multifactorial degenerative joint disease with growing prevalence in aging and obese populations, leads to disabling pain. Traditionally viewed as mechanically driven, increasing research implicates systemic inflammation and metabolic and neuroimmune modulation. The gut microbiome—an ecosystem of commensal organisms regulating host immune, metabolic, and inflammatory regulation—has emerged as a potential contributor to OA pathogenesis and symptom severity. This review aims to synthesize literature evaluating associations between gut microbiota composition and knee OA, focusing on inflammatory pathways, pain modulation, and emerging therapies. Methods A literature search was conducted using PubMed, Embase, Scopus, and Web of Science. Inclusion criteria of the English language and examining knee OA pain associations with microbiota composition yielded 16 articles. Outcomes included microbial diversity, endotoxin levels, inflammatory pathways, and microbiome-targeted interventions (prebiotics/probiotics). Results Individuals with knee OA exhibited altered gut microbiota composition compared to controls, with reduced diversity and shifts towards pro-inflammatory taxa. These changes correlate with elevated inflammatory markers and may influence joint pain and cartilage integrity. Mendelian randomization studies suggest causal links between specific microbial taxa and chronic regional pain, including knee OA. In preclinical murine models, particular species mitigated OA-related pain, cartilage degradation, and gut dysbiosis, with associated reductions in pro-inflammatory mediators and restoration of beneficial bacteria. Some clinical trials demonstrated that prebiotics and probiotics improved function, reduced inflammatory markers, and modulated gut flora. Conclusions The gut microbiome may influence the development and progression of knee OA via systemic inflammatory and metabolic pathways. Microbiome-directed therapies may serve positive clinical implications for OA management, though further research is needed to establish causal relationships.