Gut microbiota dysbiosis linked to osteoarthritis pathology in preclinical and human studiesGut health may play a role in osteoarthritis joint pain

Osteoarthritis (OA) is increasingly recognised as a whole-joint disease driven by biomechanical stress, metabolic dysfunction, low-grade inflammation and immune dysregulation, yet effective disease-modifying treatments remain unavailable. Growing evidence suggests that gut microbiota dysbiosis may contribute to OA pathogenesis, giving rise to the concept of a functional and potentially targetable gut–joint axis. In this narrative review, we synthesise current evidence linking gut microbial alterations to OA and highlight the immunological mechanisms through which intestinal dysbiosis may influence joint degeneration. Human studies have identified OA-associated changes in gut microbial composition and microbial metabolites, whereas preclinical models, germ-free experiments and faecal microbiota transplantation studies provide mechanistic support for a contributory role of dysbiosis in cartilage damage, synovitis and subchondral bone remodelling. Gut dysbiosis can impair intestinal barrier integrity, facilitate systemic exposure to microbial products such as lipopolysaccharide, disturb short-chain fatty acid, bile acid and tryptophan-derived metabolite profiles, and alter enteroendocrine and immune signalling. These processes may activate Toll-like receptor, NF-κB, NLRP3 inflammasome, aryl hydrocarbon receptor and JAK/STAT pathways, thereby reshaping macrophage polarisation, Th17/Treg balance, mucosal IgA responses, innate lymphoid cell and γδT-cell activity, immunosenescence and low-grade systemic inflammation. Through these interconnected immune-metabolic pathways, the gut microbiota may influence cartilage catabolism, synovial inflammation, subchondral bone remodelling and inflammation-related pain. Microbiome-derived taxa, metabolites and host–microbe immune signatures might support risk assessment, endotype stratification and therapeutic monitoring; however, causality in humans remains incompletely established, and current findings are limited by heterogeneity in OA phenotypes, microbiome methods, host metabolic status and clinical endpoints. Microbiota-targeted strategies remain promising adjuncts rather than established disease-modifying treatments. Future studies should integrate standardised microbiome profiling, immune phenotyping, multi-omics approaches, longitudinal cohorts and rigorously designed clinical trials to translate gut–joint axis biology into microbiome-informed precision care for OA.