Mechanistic insights into gut microbiota-driven autoimmunity in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose pathogenic drivers and initiating immune events remain incompletely understood. Increasing evidence implicates the gut-joint axis in RA, yet the mechanisms by which intestinal microbiota contribute to disease development still require integrative clarification. This review summarizes current experimental and clinical evidence on the role of gut dysbiosis in promoting autoimmunity in RA. We discuss alterations in microbial composition and their links to barrier dysfunction, immune-cell polarization, microbial metabolites, and antigen-specific immune responses. Human cohort studies and arthritis models suggest that reduced microbial diversity, loss of short-chain fatty acid (SCFA)-producing commensals, and expansion of taxa such as Prevotella copri and Collinsella are associated with impaired epithelial integrity, enhanced Th17/Tfh differentiation, reduced regulatory T- and B-cell activity, and increased autoantibody production. Mechanistic studies further support roles for molecular mimicry, microbially derived citrullinated antigens, and metabolite-mediated signaling in the breakdown of immune tolerance and persistence of synovial inflammation. We also discuss emerging microecology-based interventions, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, together with their translational potential and current limitations. Overall, available evidence places gut microbiota-mediated immune remodeling at the center of RA pathogenesis and supports precision microbiome modulation as a promising adjunctive strategy for disease prevention and treatment.