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Oral Microbiota Identifies Patients in Early Onset Rheumatoid Arthritis 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: 2021

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 evaluated the composition of the oral microbiota in untreated patients with early-onset rheumatoid arthritis (eRA), comparing it to age- and sex-matched healthy controls. The investigation employed multiplex 16S rRNA gene sequencing on saliva samples to identify microbial shifts associated with eRA, both with and without clinically defined periodontal disease. The analysis also included functional profiling via PICRUSt to determine whether predicted metabolic functions differed between the groups.

Who was studied?

The study included 61 patients diagnosed with early-onset rheumatoid arthritis (symptom duration ≤12 months) and 59 healthy controls. None of the patients had begun disease-modifying anti-rheumatic drug therapy. Participants were classified by periodontal status to assess whether microbial differences were independent of underlying periodontal disease. Smoking, corticosteroid use, and other demographic factors were also recorded to assess confounders.

What were the most important findings?

The study revealed significant compositional and functional differences in the oral microbiota between eRA patients and controls. Saliva samples from eRA patients showed higher species richness and a more dispersed microbial profile. Notably, species enrichment included Prevotella pleuritidis, Porphyromonas endodontalis, Filifactor alocis, and Treponema denticola, all of which are strongly associated with periodontitis and inflammation. Importantly, these differences persisted regardless of the presence of periodontal disease. Functional predictions indicated increased pathways related to ornithine metabolism, glucosylceramidase activity, and beta-lactamase resistance, suggesting a pro-inflammatory and immunomodulatory shift in the microbial community. From a microbiome signatures perspective, Filifactor alocis emerged as a Major Microbial Association (MMA) due to its consistent elevation and known mechanistic involvement in arginine metabolism and ornithine production, both linked to citrullination—a process implicated in RA pathogenesis.

Microbial Feature or FunctioneRA Patients (Enriched or Altered)Clinical or Mechanistic Relevance
Filifactor alocisEnrichedArginine metabolism → ornithine; inflammation and RA induction
Porphyromonas endodontalisEnrichedPeriodontal pathogen; linked to Sjögren’s and systemic inflammation
Prevotella pleuritidisEnrichedPeriodontitis-associated; pro-inflammatory
Treponema denticolaEnrichedKnown periodontal pathogen; immune-modulatory
Functional PathwaysOrnithine metabolism, beta-lactamase resistance, glucosylceramidaseAssociated with inflammation, immune activation, and metabolic stress in RA
Microbial DiversityHigher in eRASuggests unstable and dysbiotic oral ecosystem
Predicted KO functionsElevated in eRAFatty acid metabolism, sphingolipid and steroid metabolism linked to immune dysregulation

What are the greatest implications of this study?

These findings offer early evidence that oral microbiota dysbiosis precedes and potentially contributes to the pathogenesis of rheumatoid arthritis. The enrichment of species such as Filifactor alocis and Porphyromonas endodontalis, coupled with shifts in microbial metabolic pathways, suggests a mechanistic link between oral microbial communities and systemic autoimmunity via processes like protein citrullination and immune activation. This supports the idea that the oral cavity may act as a trigger site in genetically susceptible individuals. Clinically, these bacterial taxa could serve as non-invasive biomarkers for eRA risk assessment, especially valuable in periodontally healthy patients, and may inform future microbiome-targeted interventions for early disease modulation.

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