Periodontal disease-associated oral and gut microbiome changes in female rheumatoid arthritis patients

Although oral and gut microbiota dysbiosis is implicated in rheumatoid arthritis (RA), their coordinated alterations across RA–periodontitis strata remain unclear. This case-control study investigated oral and gut microbiome perturbations in female RA patients stratified by periodontitis severity and their clinical correlations. Thirty-two female RA patients and thirty-three matched healthy controls (stratified into mild [MP]/severe periodontal disease [SP] groups) were included. 16 S rRNA sequencing of saliva, subgingival plaque, and stool samples was performed. Microbial composition and functional pathways were analyzed via QIIME2 and PICRUSt2. Spearman correlation analysis was performed to assess correlations between microbe abundances and clinical indices. Statistical analyses were conducted using SPSS (v22.0) and GraphPad Prism (v9), with statistical significance set at P < 0.05. The final cohort comprised 65 female participants, with RA patients having a mean age of 48.09 ± 10.96 years and healthy controls 47.97 ± 11.79 years. Based on RA status and periodontal condition, participants were stratified into four groups: 17 RA patients with mild periodontitis (RA-MP), 15 with severe periodontitis (RA-SP), 16 healthy controls with mild periodontitis (N-MP), and 17 with severe periodontitis (N-SP). Analysis of microbial α-diversity revealed no significant differences between groups across all sample types. In contrast, β-diversity analysis showed significant separation in the salivary microbiota between RA patients and controls (PERMANOVA: R²=0.039, P = 0.008), with this effect being most pronounced in the SP subgroup (R²=0.077, P = 0.003). At the genus level, LEfSe analysis identified significant enrichment of Prevotella and Streptococcus in RA saliva, while controls were enriched in Neisseria. Notably, correlation analysis demonstrated that saliva-specific Porphyromonas abundances showed positive correlations with both periodontal and rheumatologic parameters, highlighting their potential clinical relevance as non-invasive biomarkers. In contrast, the abundance of the gut genus Fusobacterium was negatively correlated with RA-related parameters, while gut Prevotella showed no significant association. Saliva-specific Porphyromonas are positively correlated with RA markers, highlighting the clinical relevance of the oral microbiota as potential noninvasive biomarkers in RA–periodontitis comorbidity. ChiCTR2500108690. This clinical trial was registered with the Chinese Clinical Trial Registry (ChiCTR) on 3 September 2025 under the registration number ChiCTR2500108690.