Mechanistic insights into gut microbiota dysbiosis in osteoarthritis based on the gut-joint axis

Abstract

Osteoarthritis (OA) is a highly prevalent degenerative joint disease characterized by articular cartilage degradation, extracellular matrix disruption, subchondral bone sclerosis, and osteophyte formation, pathological features that collectively impair joint function and significantly reduce patients’ quality of life. Therefore, elucidating the systemic pathogenic mechanisms of OA is essential for enabling early diagnosis and implementing disease modifying interventions. Recent studies demonstrate that the gut microbiota, as a key regulatory factor, actively participates in OA pathogenesis via the bidirectional “gut-joint axis.” Gut microbiota dysbiosis, including depletion of beneficial commensal bacteria, Th17/Treg imbalance, aberrant macrophage polarization, and impaired intestinal barrier integrity, disrupts host microbiota symbiosis and promotes low-grade systemic inflammation, thereby amplifying synovial inflammation, cartilage catabolism, and subchondral bone remodeling. Although accumulating evidence robustly links gut dysbiosis to OA progression, the precise molecular and cellular mechanisms, particularly how specific alterations in gut microbiota composition and metabolites contribute to OA onset and development, remain incompletely defined. This article summarizes current insights into the gut-joint axis in OA and OA-related risk factors, focusing on structural alterations in the gut microbiota and shifts in key metabolites driven by intestinal dysbiosis in OA. Based on this, targeting the gut microbiota is proposed as a promising therapeutic strategy for OA.