Periodontitis Salivary Microbiota Exacerbates Murine Rheumatoid Arthritis via Gut Dysbiosis and Immune Dysregulation

The mechanistic link between periodontitis (PD) and rheumatoid arthritis (RA) remains poorly understood. This study aimed to investigate whether PD-associated salivary microbiota exacerbates RA via an "oral-gut-immune axis." We performed 16S rRNA sequencing and untargeted metabolomics on saliva from healthy controls and patients with PD, RA, or both (PD-RA). Salivary microbiota from PD patients or healthy controls were transplanted into collagen-induced arthritis (CIA) mice. Clinically, PD-RA patients exhibited enrichment of periodontal pathogens (e.g., Porphyromonas sp., Prevotella sp.) and pro-inflammatory lipid metabolites. In vivo, transplantation of PD microbiota into CIA mice significantly worsened arthritis, evidenced by higher clinical scores (3.5 ± 0.5 vs. 2.3 ± 0.4, p < 0.05) and greater joint destruction. Mechanistically, PD microbiota colonized the gut, impaired intestinal barrier integrity, and induced systemic immune dysregulation, characterized by an increased splenic Th17/Treg cell ratio and elevated serum IL-6 and C-reactive protein. These changes were associated with altered gut microbial metabolism, including reduced short-chain fatty acids and enhanced arachidonic acid pathways. Our findings delineate a pathogenic oral-gut-immune axis in which PD microbiota aggravates RA, underscoring the importance of integrated oral and systemic disease management.