Dysbiotic Subgingival Microbial Communities in Periodontally Healthy Patients With Rheumatoid Arthritis Original paper
Researched by:
-
Kimberly Eyer
ID
Kimberly Eyer
Kimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.
-
Rheumatoid Arthritis
Rheumatoid Arthritis
OverviewRheumatoid arthritis (RA) is a systemic autoimmune disease marked by chronic joint inflammation, synovitis, and bone erosion, driven by Treg/Th17 imbalance, excessive IL-17, TNF-α, and IL-1 production, and macrophage activation. Emerging evidence links microbial dysbiosis and heavy metal exposure to RA, [1][2] with gut microbiota influencing autoimmune activation via Toll-like receptor (TLR) signaling, inflammasome activation, […]
-
Kimberly Eyer
Researched by:
-
Kimberly Eyer
ID
Kimberly Eyer
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Kimberly Eyer
What was studied?
This study investigated whether the subgingival microbiota in patients with rheumatoid arthritis (RA) differs from that of healthy individuals, independent of periodontal disease. Because periodontitis itself profoundly alters the oral microbiome, the authors specifically recruited periodontally healthy individuals to isolate the effect of RA on subgingival microbial composition. Using 16S rRNA gene sequencing and advanced bioinformatics (QIIME, PhyloToAST, and PICRUSt), the researchers assessed microbial diversity, structure, and predicted functional pathways. They also applied network graph theory to identify co-occurrence patterns and keystone taxa.
Who was studied?
The study enrolled 22 RA patients and 19 age- and sex-matched non-RA controls, all of whom were periodontally healthy. Exclusion criteria included recent antibiotic use, smoking, and overt periodontal disease. Detailed clinical periodontal measures confirmed minimal probing depth, attachment loss, and bleeding on probing across all participants. RA patients were characterized further by disease activity scores, ESR, and ACPA levels, providing a robust context for interpreting microbial shifts.
What were the most important findings?
RA patients harbored a distinct subgingival microbial community that differed significantly in both membership and structure from that of non-RA controls. Nearly 42% of the microbial community differed in abundance, and 19% in taxonomic membership. Unlike the sparse, congeneric networks of healthy individuals, RA-associated microbiota formed dense, intergeneric co-occurrence hubs dominated by anaerobic gram-negative taxa. Notably enriched genera in RA included Cryptobacterium, Fretibacterium, Desulfovibrio, Treponema, and Prevotella, many of which are capable of producing inflammatory mediators or citrulline, a post-translational modification implicated in RA autoantigen formation. Among them, Cryptobacterium curtum emerged as a prominent taxon with a 100-fold greater abundance and 39-fold higher odds of detection in RA. This species produces citrulline via arginine metabolism, potentially linking the microbiome to autoantigen generation. Network analysis also highlighted metabolic pathways related to arachidonic acid and ether lipid metabolism, aligning microbial function with RA-associated inflammation.
| Category | Findings in RA Patients | Clinical/Functional Implications |
|---|---|---|
| Community Structure | 42% differed in abundance; 19% in membership | Indicates RA alters microbiome independent of periodontitis |
| Enriched Genera | Cryptobacterium, Fretibacterium, Treponema, Desulfovibrio, Prevotella | Linked to inflammation and citrullination |
| Core Microbiome Differences | 38 unique RA species in ≥80% of patients | Suggests stable microbial signature in RA |
| Not Significant Between Groups | Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans | Challenges assumption of their exclusivity in RA etiology |
| Network Topology | Highly connected intergeneric hub; 83 core species | Indicates coordinated microbial activity under RA influence |
| Functional Prediction | ↑ Arachidonic acid and ether lipid metabolism pathways | Supports inflammatory contribution of RA oral microbiota |
| Notable Species | Cryptobacterium curtum (100× enriched, 39× odds) | Potential contributor to citrullinated autoantigen formation in RA |
What are the greatest implications of this study?
This study underscores the role of RA as a selective pressure on the oral microbiome, even in the absence of clinical periodontitis. The identification of a robust, RA-specific subgingival microbiome—enriched for pro-inflammatory and citrulline-producing taxa—suggests microbial contributions to RA pathogenesis beyond established periodontal pathogens like P. gingivalis and A. actinomycetemcomitans, which were not significantly different between groups. The tight interconnectivity among gram-negative anaerobes and the shared enrichment in metabolic pathways involved in inflammation imply a potential ecological and immunological role for the oral microbiome in driving systemic autoimmunity. C. curtum in particular warrants further investigation as a potential biomarker or microbial driver of RA. These findings support a microbiome-targeted approach to RA risk assessment and early intervention, especially in individuals with genetically or serologically defined risk.