Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis Original paper
Researched by:
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Kimberly Eyer
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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.
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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, […]
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Kimberly Eyer
Researched by:
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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 oral microbiota dysbiosis in individuals at high risk for rheumatoid arthritis (RA), patients with established RA, and healthy controls. By examining salivary samples, the researchers aimed to determine whether microbial alterations precede the clinical onset of RA and to identify microbial signatures associated with systemic autoimmunity. The study leveraged 16S rRNA gene sequencing to characterize the microbial community structure and its associations with anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) levels.
Who was studied?
A total of 79 participants were recruited from West China Hospital. These included 29 high-risk individuals who were ACPA-positive without clinical arthritis, 27 RA patients, and 23 healthy controls. All participants were age- and gender-matched. The RA patients were mostly receiving disease-modifying antirheumatic drugs and corticosteroids, while the high-risk individuals were treatment-naïve. None of the participants had used antibiotics or probiotics recently, and all were screened for autoimmune and gastrointestinal comorbidities.
What were the most important findings?
The study found that oral microbiota dysbiosis is evident in the pre-clinical stage of RA. High-risk individuals exhibited significantly reduced microbial diversity and compositional shifts compared to healthy controls and RA patients. Notably, the genera Rothia and Prevotella_6 were enriched in high-risk individuals, while Neisseria oralis and Defluviitaleaceae_UCG-011 were depleted. Prevotella_6 abundance increased progressively from healthy controls to high-risk individuals to RA patients, suggesting its role in disease transition. Importantly, P. gingivalis, a known periodontal pathogen implicated in RA, was paradoxically decreased in high-risk individuals. The study also uncovered correlations between specific genera and serum levels of ACPA and RF. For instance, Eubacterium nodatum_group and Tannerella were positively associated with ACPA in high-risk individuals, whereas Neisseria showed an inverse correlation. RA patients displayed additional shifts, including elevated Actinomyces and Lactobacillus, the latter of which correlated positively with ESR and CRP, linking microbial perturbation to systemic inflammation.
| Key Finding | Microbial Associations | Clinical Implications |
|---|---|---|
| Reduced diversity in high-risk individuals | ↓ Neisseria oralis, ↓ Defluviitaleaceae_UCG-011 | Suggests early dysbiosis precedes RA symptoms |
| Enrichment of Rothia and Prevotella_6 | ↑ Rothia, ↑ Prevotella_6 | Potential biomarkers for RA progression |
| Autoantibody correlations in high-risk group | ↑ Tannerella, Eubacterium nodatum_group | Correlate with ACPA titers, linking microbes to immune activation |
| Functional prediction differences (KEGG) | ↑ Bacterial toxin, ↓ fatty acid biosynthesis | Suggests proinflammatory metabolic profiles in RA oral microbiome |
| ROC curve for biomarker panel (11 genera) | Prevotella_6, Actinomyces, Rothia, others | Achieved AUC of 0.8; potential for early RA detection |
What are the greatest implications of this study?
The findings support the hypothesis that oral microbiota dysbiosis is not merely a consequence of RA but may play a role in its pathogenesis. The distinct microbial shifts in high-risk individuals suggest that dysbiosis may contribute to immune priming and autoantibody production before clinical symptoms emerge. This aligns with the mucosal origin theory of RA. The identification of microbial genera such as Rothia and Prevotella_6 as potential early biomarkers provides a foundation for predictive models and microbiome-targeted interventions. Moreover, the correlation of microbial taxa with immunological markers underscores the potential of oral microbiota as a non-invasive diagnostic tool and as a mechanistic contributor to disease development. These insights could pave the way for preventive strategies in at-risk populations, including modulation of oral microbiota to delay or prevent RA onset.