Enterococcus gallinarum and Lupus: A Possible Gut-Autoimmune Connection

By SWA

Related to: Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human
https://www.science.org/doi/10.1126/scitranslmed.adj6294?url_ver=Z39.88-2003

Autoimmune diseases like systemic lupus erythematosus (SLE) have long been linked to immune system dysfunction, but recent research suggests that gut bacteria may also play a role. One bacterium of particular interest is Enterococcus gallinarum, a gut microbe that can escape the intestines and trigger immune responses. While scientists have established its ability to drive autoimmunity in mice, its exact impact on human autoimmune diseases like lupus remains an area of active research.

The Link Between Enterococcus gallinarum and Lupus

A recent study found that E. gallinarum activates specific immune pathways in human blood cells. It increases levels of key immune molecules—interferon-γ (IFN-γ) and IL-17—while also stimulating immune cells such as monocytes. Additionally, E. gallinarum triggers the production of IgG3 antibodies against bacterial RNA.

Interestingly, patients with lupus and autoimmune hepatitis showed high levels of these same IgG3 antibodies, not only against E. gallinarum but also against their own RNA. This suggests a potential connection between the presence of E. gallinarum and the development of autoimmune responses in humans.

How to Test for E. gallinarum and Related Immune Markers

Diagnosing the presence of E. gallinarum and its impact on the immune system requires a combination of microbiological and immunological tests.

1. Testing for Enterococcus gallinarum

✅ Stool or Blood Culture – Identifies E. gallinarum by growing it from a sample on specialized agar.
✅ PCR (Polymerase Chain Reaction) – Detects E. gallinarum DNA in stool, blood, or tissue samples.
✅ 16S rRNA Sequencing – Analyzes bacterial RNA to confirm the presence of E. gallinarum.

2. IgG3 Antibodies (Against E. gallinarum and Human RNA)

✅ ELISA (Enzyme-Linked Immunosorbent Assay) – Measures IgG3 antibody levels in blood.
✅ Western Blot – Confirms the presence of IgG3 antibodies.
✅ Immunofluorescence Assay (IFA) – Uses fluorescent markers to visualize IgG3 antibodies binding to bacterial or human RNA.

3. Interferon-γ (IFN-γ) Testing

✅ ELISA or Multiplex Cytokine Assay – Measures IFN-γ in blood serum.
✅ qPCR (Quantitative PCR) – Detects IFN-γ gene expression in immune cells.
✅ Flow Cytometry – Identifies IFN-γ-producing immune cells.
✅ ELISpot (Enzyme-Linked ImmunoSpot) – Identifies IFN-γ-secreting cells.

4. IL-17 Testing

✅ ELISA or Multiplex Cytokine Assay – Measures IL-17 levels in blood.
✅ qPCR – Evaluates IL-17 gene expression.
✅ Flow Cytometry – Detects IL-17-producing immune cells.
✅ ELISpot – Identifies individual IL-17-secreting cells.

These tests help determine whether E. gallinarum is present and if it is triggering an abnormal immune response.

Treatment Approaches

If E. gallinarum contributes to autoimmunity, treatment can focus on reducing bacterial overgrowth, preventing translocation, and managing immune responses.

1. Treating E. gallinarum Overgrowth or Translocation

✅ Antibiotics – Although E. gallinarum is resistant to some antibiotics (like vancomycin), it may be treated with:

  • Chloramphenicol
  • Linezolid
  • Daptomycin
  • Tetracyclines (e.g., doxycycline)
    ✅ Probiotics & Gut Health Support – Beneficial bacteria (Lactobacillus, Bifidobacterium) may help balance the microbiome.
    ✅ Fecal Microbiota Transplant (FMT) – In severe cases, gut bacteria from a healthy donor can restore balance.
    ✅ Dietary Changes – A low-inflammatory diet (Mediterranean, anti-inflammatory) may help manage symptoms.

2. Managing the Autoimmune Response

✅ Immunosuppressive or Immunomodulatory Therapies

  • Corticosteroids (e.g., prednisone) – Reduce inflammation.
  • Biologics (e.g., IL-17 inhibitors like secukinumab, IFN-γ blockers, or TNF inhibitors) – Target specific immune pathways.
  • Methotrexate or Mycophenolate mofetil – Commonly used for lupus treatment.
    ✅ Anti-Inflammatory Medications – NSAIDs (e.g., ibuprofen) or low-dose aspirin may help with inflammation.
    ✅ Lifestyle Adjustments – Regular exercise, stress management, and a healthy diet support immune balance.

3. Future & Experimental Therapies

🔹 TLR8 Inhibitors – May prevent the immune system from overreacting to E. gallinarum.
🔹 Targeted Microbiome Therapy – Engineered probiotics or bacteriophages could selectively eliminate E. gallinarum.

Conclusion

The potential role of Enterococcus gallinarum in lupus and other autoimmune diseases is an emerging area of research. While it is clear that this bacterium can influence immune responses, more studies are needed to determine if targeting E. gallinarum could help prevent or treat lupus in humans. For now, a combination of gut health management and immune regulation remains the best approach for those affected.

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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