Gut Microbial Composition and Function Are Altered in Patients with Early Rheumatoid Arthritis Original paper
Researched by:
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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.
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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
Location
South Korea
Sample Site
Feces
Species
Homo sapiens
What was studied?
This study examined the gut microbiome in female patients with early rheumatoid arthritis (RA), including both preclinical and clinically apparent cases, compared to healthy female controls. Using 16S rRNA sequencing, the authors evaluated differences in microbial composition, diversity, and predicted functional pathways. The goal was to identify microbial shifts specific to early RA and their potential mechanistic contributions to disease onset and progression.
Who was studied?
The cohort included 29 Korean women with early RA—17 with preclinical RA and 12 with clinically apparent RA—and 25 age-matched healthy female controls. RA patients had not received disease-modifying antirheumatic drugs (DMARDs), minimizing confounding pharmaceutical effects. Participants were excluded if they had taken antibiotics, probiotics, or prebiotics recently. Disease activity, including DAS28, CRP, and ESR levels, was also recorded and correlated with microbial features.
What were the most important findings?
The gut microbiome in early RA patients showed significantly reduced alpha diversity and distinct beta diversity compared to healthy controls, suggesting early disruption of microbial community structure. Taxonomic profiling identified an enrichment of Bacteroidetes (particularly Prevotella) in RA patients, while Actinobacteria, especially the genus Collinsella and Bifidobacterium, were depleted. Prevotella’s overrepresentation is consistent with prior studies associating it with Th17-mediated inflammation. Functional prediction using PICRUSt revealed enrichment of iron acquisition genes (e.g., siderophore receptors) in RA patients, aligning with the anemia and heightened iron demand typical in RA. Conversely, genes involved in menaquinone (vitamin K2) biosynthesis, often linked to anti-inflammatory gram-positive bacteria, were enriched in healthy controls. Interestingly, preclinical and symptomatic RA patients had similar microbial compositions, but only symptomatic RA patients showed enrichment of LPS synthesis genes, correlating with elevated DAS28 scores and suggesting a role in systemic inflammation. These findings highlight Collinsella and Bifidobacterium depletion and Prevotella expansion as Major Microbial Associations (MMAs) in early RA.
| Feature | Observation in Early RA | Clinical or Microbial Implication |
|---|---|---|
| Alpha Diversity | Decreased | Indicates early microbial dysbiosis |
| Prevotella (Bacteroidetes) | Enriched | Associated with Th17-driven inflammation |
| Collinsella (Actinobacteria) | Depleted | Potential loss of gut integrity, linked to immune modulation |
| Bifidobacterium | Depleted | Anti-inflammatory, supports gut health; reduced in RA patients |
| Iron Transport Genes (COG1629) | Enriched | Suggests siderophore-mediated iron competition and links to RA anemia |
| Menaquinone Biosynthesis Genes | Depleted | Indicates loss of gram-positive, anti-inflammatory functions |
| LPS Synthesis Genes (COG2148) | Elevated in symptomatic RA | Correlated with DAS28, indicating microbial contribution to disease severity |
What are the greatest implications of this study?
This study reinforces the central role of the gut microbiome in early rheumatoid arthritis pathogenesis, even before clinical onset. The identification of microbial signatures and functional traits such as iron metabolism and LPS biosynthesis provides mechanistic insight into how dysbiosis may modulate immune responses and systemic inflammation. The findings suggest that specific taxa, including Prevotella and Collinsella, may serve as early microbial biomarkers or therapeutic targets. Importantly, the enrichment of pro-inflammatory pathways in clinically apparent RA but not preclinical stages implies that microbial function, not just composition, influences disease transition and severity. This supports the future development of microbiome-targeted interventions for RA prevention and therapy, particularly in at-risk or early-stage patients.