The Gut Microbiome and Rheumatoid Arthritis: A Hidden Driver of Autoimmunity and an Emerging Therapeutic Target

Rheumatoid arthritis (RA) is a chronic, systemic, immune-mediated inflammatory disease characterized by persistent synovitis, progressive joint destruction, functional disability, and a wide spectrum of extra-articular manifestations. Despite substantial advances in disease-modifying therapies, RA continues to impose a significant global health burden, with rising prevalence and substantial socioeconomic costs. In recent years, growing attention has been directed toward the gut–immune axis, revealing the gut microbiota as a central regulator of immune homeostasis and a potential driver of autoimmune diseases, including RA. Accumulating evidence from animal models, human cohort studies, and translational research indicates that alterations in gut microbial composition and function—collectively referred to as dysbiosis—may precede clinical disease onset, influence immune tolerance, and modulate disease severity and therapeutic response. This comprehensive review integrates current knowledge on the epidemiology, etiology, immunopathogenesis, and systemic manifestations of RA, with a particular emphasis on the mechanistic and translational role of the gut microbiome. We discuss microbial–host interactions, immune pathways, emerging microbiome-derived biomarkers, and evolving microbiota-targeted therapeutic strategies, highlighting their potential to reshape the future of personalized RA management.