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Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis Original paper

Researched by:

  • Kimberly Eyer ID
    Kimberly Eyer

    User avatarKimberly 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.

May 20, 2025

  • 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, […]

Researched by:

  • Kimberly Eyer ID
    Kimberly Eyer

    User avatarKimberly 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.

Last Updated: 2022

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

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.

What was studied?

This study investigated the subgingival microbiome in rheumatoid arthritis (RA) patients with periodontitis in a Taiwanese population. It aimed to characterize the compositional and functional differences in subgingival microbial communities between RA patients and matched healthy controls using 16S rRNA gene sequencing. The primary goal was to evaluate correlations between specific microbial taxa and levels of anti-citrullinated protein antibodies (ACPAs), which are hallmark autoantibodies in RA.

Who was studied?

Subjects included RA patients with periodontitis and matched control groups. Subgingival plaque samples were collected and categorized into three clinical groups: individuals with active periodontitis (PD), those with active RA and periodontitis (AM), and periodontally healthy individuals. The final analysis focused on the AM and PD groups for microbial profiling and immunologic correlations with ACPAs.

What were the most important findings?

The study revealed significant differences in subgingival microbiota between RA patients and controls. In both AM and PD groups, Aminipila butyrica and Peptococcus simiae were enriched in RA patients and showed positive correlations with serum ACPA levels. A. butyrica, a strictly anaerobic, arginine-decomposing bacterium, encodes arginine deiminase, facilitating the production of citrulline—potentially leading to the formation of citrullinated antigens that induce ACPA production. This mechanism parallels that of P. gingivalis and supports its role as a potential Major Microbial Association (MMA) in RA.

Peptostreptococcus stomatis also demonstrated a strong positive correlation with ACPA levels and has been implicated in autoimmune processes, likely due to its ability to initiate NETosis and hypercitrullination via pore-forming toxins. Additionally, Streptococcus sanguinis was associated with increased ACPA levels in the PD group, while Pseudomonas batumici showed a negative correlation. PICRUSt2 functional prediction highlighted enrichment in arginine, ornithine, and proline interconversion pathways in RA patients, particularly those involving L-citrulline metabolism.

Microbial TaxaCorrelation with ACPAProposed Mechanism
Aminipila butyricaPositive (AM & PD groups)Arginine deiminase → citrulline → ACPA induction
Peptococcus simiaePositive (AM & PD groups)Potential PAD activation via NETosis
Peptostreptococcus stomatisStrong positive (AM)Immune-inflammatory trigger; linked to autoimmunity
Streptococcus sanguinisPositive (PD group)Possible secondary contributor to ACPA production
Pseudomonas batumiciNegative (PD group)Enriched in controls; potential protective role
Pathways (PICRUSt2)Enriched in RA (AM & PD)Arginine/proline metabolism → L-citrulline biosynthesis

What are the greatest implications of this study?

This study highlights a mechanistic link between subgingival dysbiosis and systemic autoimmunity in RA, particularly through bacteria capable of driving citrullination. The enrichment of A. butyrica and P. simiae, coupled with elevated ACPAs, supports the hypothesis that periodontal microbiota contribute to RA pathogenesis through microbial or host protein citrullination. These findings underscore the diagnostic and therapeutic potential of targeting oral microbial communities—particularly those expressing arginine deiminase or capable of inducing NETosis—in RA patients. From a microbiome signatures perspective, A. butyrica, P. simiae, and P. stomatis are high-confidence MMAs that may serve as predictive biomarkers or targets for MBTIs, especially those modulating arginine metabolism or immunogenic bacterial citrullination.

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