Rheumatoid Arthritis
Rheumatoid arthritis (A) is a systemic autoimmune disease marked by chronic joint inflammation, synovitis, and bone erosion, driven by Th17 imbalance, excessive L-17, NF-α, and L-1 production, and macrophage activation. Emerging evidence links microbial dysbiosis and heavy metal exposure to A, [1][2] with gut microbiota influencing autoimmune activation via Toll-like receptor (LR) signaling, inflammasome activation, […]
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Karen Pendergrass
Overview 
Microbiome Signature 
Research Feed 
Interventions 
References Overview
Rheumatoid 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, and molecular mimicry, contributing to systemic immune dysfunction.
Associated Conditions
Conditions such as periodontitis, autoimmune thyroid disorders (Hashimoto’s, Graves’), multiple sclerosis (MS), and inflammatory bowel disease (IBD). RA is also linked to nonalcoholic fatty liver disease (NAFLD), fibromyalgia, and chronic fatigue syndrome (CFS). These associations highlight RA’s systemic complexity beyond joint inflammation.
Causes
Rheumatoid arthritis (RA) is a complex, multifactorial disease influenced by genetic predisposition, immune dysregulation, environmental exposures, and metabolic factors. While traditional theories emphasize the role of HLA-DR4 and HLA-DR1 genetic risk factors, along with autoantibody production and inflammatory cytokines such as TNF-α, IL-6, and IL-1β, a more holistic approach integrates emerging insights into microbial-metal interactions and their contribution to disease progression. Heavy metal dysregulation, in particular, has been implicated in immune dysfunction, oxidative stress, and the disruption of gut and oral microbiota, which collectively exacerbate RA pathogenesis.
Primer
Microbial-metal interactions play a significant role in the pathogenesis of rheumatoid arthritis (RA), with heavy metal dysregulation contributing to immune dysregulation and oxidative stress. High soil copper (Cu) exposure has been correlated with increased inflammation in RA patients, with Cu levels positively associated with erythrocyte sedimentation rate (ESR), platelet count, and disease activity (DAS28). [3] Lead (Pb) and cadmium (Cd) further exacerbate immune dysfunction, with Cd inhibiting superoxide dismutase, thereby reducing antioxidant defenses and increasing joint damage. [4][5] Elevated nickel (Ni) levels in RA patients have been linked to inflammasome activation, while increased chromium (Cr) concentrations affect immune tolerance and oxidative stress. [6] Additionally, microbial dysbiosis influences metal homeostasis, as Porphyromonas gingivalis enhances metal-driven citrullination, accelerating autoimmunity. [7] Gut microbial shifts, particularly Prevotella overgrowth and Akkermansia depletion, further impact metal absorption and immune function, reinforcing the intricate relationship between heavy metal exposure, microbial imbalances, and RA pathogenesis. [8]
Metal Homeostasis in RA
| Metal | Mechanism |
|---|---|
| Copper (Cu) | Promotes IL-6, TNF-α, neutrophil activation. [9] |
| Lead (Pb) | Induces ROS, disrupts immune tolerance. [10] |
| Cadmium (Cd) | Inhibits SOD, increases oxidative stress. [11] |
| Nickel (Ni) | Induces IL-1β, Th17 responses. [13] |
| Chromium (Cr) | Alters mitochondrial function, immune suppression. [14] |
Microbiome Signature: Rheumatoid Arthritis
Major Microbial Associations
Major Microbial Associations in RA patients:
| Increased Microbes (Pathobionts) | Decreased Microbes (Protective) & Viruses |
|---|---|
| Prevotella dentalis | Rothia dentocariosa |
| Prevotella denticola | Faecalibacterium prausnitzii |
| Treponema dentalis | Granulicatella |
| Selenomonadales | Veillonella rogosae |
| Selenomonas | Lactobacillus gasseri |
| Prevotella | |
| Epstein-Barr virus (EBV) | |
| Actinomyces | |
| Tannerella | |
| Treponema |
Research Feed
Role of Some Heavy Metals in Rheumatoid Arthritis
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Analyzing the impact of heavy metal exposure on osteoarthritis and rheumatoid arthritis: an approach based on interpretable machine learning
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A comparative study of the gut microbiota in immune-mediated inflammatory diseases-does a common dysbiosis exist?
December 13, 2018
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Autoimmune Diseases •
Autoimmune Diseases
Did you know?
Americans are over three times more likely to suffer from autoimmune diseases compared to the global average, with approximately 16.67% of the U.S. population affected versus 5% worldwide.
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Interventions
Microbiome-targeted interventions offer a promising avenue for modulating immune responses in rheumatoid arthritis (RA), with probiotic therapy emerging as a potential intervention. Parabacteroides histicola has been shown to restore regulatory T cell (Treg) function, counteracting the pro-inflammatory effects of T helper 17 (Th17) cells, which play a central role in RA pathogenesis. By promoting immune tolerance and reducing systemic inflammation, P. histicola may help mitigate disease progression, offering a microbiome-based approach to complement conventional treatments.
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References
- Role of Some Heavy Metals in Rheumatoid Arthritis.. Arshad, M. ., Riaz, N. ., Bashir, R. ., Irfan, S. ., Khan, S. Y. ., & Tahir, H. M.. (Research Developments in Medicine and Medical Science Vol. 7, 44–50. 2023.)
- Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.. Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.. (Iran J Public Health. 2017)
- Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.. Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.. (J Formos Med Assoc. 2016)
- Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.. Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.. (Iran J Public Health. 2017)
- Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.. Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.. (2024.)
- Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.. Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.. (J Formos Med Assoc. 2016)
- Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.. Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.. (Iran J Public Health. 2017)
- Analyzing the impact of heavy metal exposure on osteoarthritis and rheumatoid arthritis: an approach based on interpretable machine learning.. Fan W, Pi Z, Kong K, Qiao H, Jin M, Chang Y, Zhang J, Li H.. (Front Nutr. 2024)
- Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.. Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.. (J Formos Med Assoc. 2016)
- Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.. Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.. (Iran J Public Health. 2017)
- Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.. Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.. (2024.)
- Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.. Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.. (2024.)
- Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.. Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.. (J Formos Med Assoc. 2016)
- Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.. Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.. (2024.)
Arshad, M. ., Riaz, N. ., Bashir, R. ., Irfan, S. ., Khan, S. Y. ., & Tahir, H. M.
Role of Some Heavy Metals in Rheumatoid Arthritis.Research Developments in Medicine and Medical Science Vol. 7, 44–50. 2023.
Read ReviewIrfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.
Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.Iran J Public Health. 2017
Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.
Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.J Formos Med Assoc. 2016
Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.
Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.Iran J Public Health. 2017
Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.
Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.2024.
Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.
Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.J Formos Med Assoc. 2016
Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.
Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.Iran J Public Health. 2017
Fan W, Pi Z, Kong K, Qiao H, Jin M, Chang Y, Zhang J, Li H.
Analyzing the impact of heavy metal exposure on osteoarthritis and rheumatoid arthritis: an approach based on interpretable machine learning.Front Nutr. 2024
Read ReviewYang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.
Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.J Formos Med Assoc. 2016
Irfan S, Rani A, Riaz N, Arshad M, Kashif Nawaz S.
Comparative Evaluation of Heavy Metals in Patients with Rheumatoid Arthritis and Healthy Control in Pakistani Population.Iran J Public Health. 2017
Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.
Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.2024.
Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.
Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.2024.
Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC.
Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper.J Formos Med Assoc. 2016
Haddad, Rana & Elbeialy, Adel & Sawy, Soaad & Elzomor, Hala.
Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activity.2024.