An expansion of rare lineage intestinal microbes characterizes 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 the gut microbiome composition and its immunological and metabolic impact in rheumatoid arthritis (RA). Using 16S rRNA sequencing, plasma metabolomics, and predictive modeling, the researchers analyzed fecal samples from RA patients, their first-degree relatives (FDRs), and healthy controls. They aimed to identify microbial signatures associated with RA and validate the functional relevance of key taxa through human epithelial cell models and a humanized mouse model of arthritis. The central objective was to elucidate the microbial and metabolite profiles predictive of RA onset and progression.
Who was studied?
The study enrolled 40 RA patients fulfilling the 2010 ACR classification criteria, 15 first-degree relatives without autoimmune symptoms, and 17 unrelated healthy controls. Exclusion criteria included antibiotic or probiotic use, gastrointestinal or other autoimmune diseases. All human participants were enrolled through the Mayo Clinic, with ethical approval and informed consent. Animal models included HLA-DQ8 transgenic mice used to confirm microbial effects on disease severity.
What were the most important findings?
The RA group exhibited significantly decreased gut microbial diversity compared to controls, a shift driven primarily by an expansion of rare taxa from the phylum Actinobacteria, notably Collinsella, Eggerthella, and Actinomyces, alongside a reduction in Faecalibacterium. Random forest models identified Collinsella, Eggerthella, and Faecalibacterium as the most predictive genera for RA. Collinsella abundance was correlated with increased IL-17A production, disrupted gut epithelial tight junctions (ZO-1), elevated intestinal permeability, and pro-inflammatory chemokine expression. Experimental validation in HLA-DQ8 mice showed increased arthritis incidence following Collinsella exposure. Metabolomic data revealed elevated levels of alpha-aminoadipic acid and asparagine in RA patients, with significant correlations to Collinsella abundance. These findings position Collinsella as a candidate pathobiont with mechanistic links to both immune modulation and mucosal barrier dysfunction.
| Key Domain | Findings | Implications |
|---|---|---|
| Major Microbial Associations (MMAs) | Collinsella, Eggerthella (enriched); Faecalibacterium (depleted) | Predict RA presence; linked to inflammation, epithelial dysfunction |
| Microbial Diversity | Reduced alpha- and beta-diversity in RA patients | Indicates dysbiosis and microbial imbalance relevant to disease state |
| Functional Validation | Collinsella increased IL-17A, gut permeability, CXCL1/5 in vitro and arthritis severity in mice | Establishes causal link between microbial taxa and RA pathology |
| Metabolomic Associations | Elevated alpha-aminoadipic acid, asparagine; correlated with Collinsella abundance | Suggests microbe-metabolite-immune axis may mediate RA progression |
| Predictive Modeling | Random forest and Boruta algorithms identified top discriminatory taxa | Validates potential for microbial biomarkers in RA diagnosis and screening |
| Therapeutic Considerations | MTX and hydroxychloroquine associated with increased microbial diversity | Microbiome recovery may mediate therapeutic effects; supports microbiome as adjunctive target |
What are the greatest implications of this study?
This study provides compelling evidence that RA is associated with dysbiosis marked by an expansion of rare microbial taxa, especially Collinsella and Eggerthella, which act as Major Microbial Associations (MMAs) influencing disease progression through immune activation and barrier disruption. The mechanistic data support Collinsella‘s contribution to gut permeability and pro-inflammatory cytokine expression, implicating it in the early pathogenesis of RA. The loss of Faecalibacterium, a butyrate-producing genus linked to epithelial health, further amplifies mucosal vulnerability. These insights endorse microbial biomarkers for RA risk stratification and underscore the therapeutic potential of microbiome modulation. Importantly, microbial features predictive of RA were not confounded by treatment regimens, enhancing their utility for diagnostic and preventive interventions.