Gut microbiota dysbiosis in rheumatoid arthritis: mechanisms linking intestinal barrier dysfunction to synovial inflammation

Abstract

Rheumatoid arthritis (RA) is a chronic, systemic, multifactorial autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Although its etiology is complex, accumulating evidence suggests that alterations in the gut microbiota may influence disease susceptibility and progression through interactions with the host immune system. Throughout this review, we discuss the gut microbiota as one component of a broader network of mechanisms contributing to RA pathogenesis rather than as the sole initiating factor. Compromised intestinal barrier integrity and microbial dysbiosis may facilitate the translocation of microbial products, promoting immune activation and loss of tolerance. These alterations have been proposed to contribute to several pathogenic mechanisms, including molecular mimicry, protein citrullination, and disruption of the Th17/Treg balance, thereby linking mucosal immune responses with synovial inflammation. Patients with RA also frequently exhibit reduced intestinal production of short-chain fatty acids (SCFAs), particularly butyrate, which is associated with decreased abundances of SCFA-producing bacteria, including Faecalibacterium and Roseburia, and lower fecal and circulating butyrate levels. Reduced SCFA availability may further exacerbate inflammatory pathways and impair immune homeostasis. In parallel, gut-imprinted immune cells may migrate to the joints through shared homing pathways, potentially amplifying local inflammation. Taken together, current evidence supports the gut–joint axis as a promising framework for understanding immune dysregulation in RA and highlights microbiota-targeted interventions as potential adjunctive therapeutic strategies.