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

Year: 2025

Type: article

Abstract: 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.

Source: The FASEB Journal

DOI: 10.1096/fj.202502610r