Category: Helminthic Therapy

Helminthic Therapy is a collection of research notes, reflections, and deeper dives into the science of therapeutic helminths. These pieces highlight studies, ideas, and perspectives that go beyond what’s covered in other resources. For complete and up-to-date information, see the Helminthic Therapy Wiki, the world’s largest information database documenting the science, management, experience, and results of helminth replacement.

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How Helminths Help Despite Elevated IL-10 in Multiple Sclerosis (MS)

How Helminths Help Despite Elevated IL-10 in Multiple Sclerosis (MS)

The Problem: Dysregulated IL-10 Production and Response in MS

The core problem with IL-10 in MS before helminth intervention is a dysregulation of IL-10 production and response, not simply its quantity. While elevated IL-10 levels are often detected in MS patients, these do not consistently translate into effective control of neuroinflammation or disease progression. Specialized IL-10-producing cells—particularly regulatory B cells (Bregs) and regulatory T cells (Tregs)—are often reduced in number or impaired in function in MS, compromising their ability to suppress pathogenic T cell subsets such as Th1 and Th17.

In addition, pro-inflammatory mediators like IL-6 are frequently elevated in MS and can interfere with IL-10 signaling pathways, inducing resistance to IL-10’s immune-suppressive effects. IL-10 produced by non-regulatory or inappropriate immune cells, or delivered at the wrong time, may even exacerbate disease by promoting survival of harmful lymphocytes. This complex regulatory imbalance means that the immune system remains skewed towards inflammation despite measurable IL-10, contributing to ongoing demyelination, neurodegeneration, and clinical symptoms.

This systemic imbalance in IL-10 biology represents a major therapeutic challenge, as attempts to increase IL-10 levels alone have yielded mixed and often disappointing results in MS treatment.

The Role of Regulatory B Cells and Their Dysfunction in MS

A crucial piece of this imbalance lies in the dysfunction of IL-10-producing regulatory B cells, also known as B10 cells. These cells play key roles in immune tolerance by secreting IL-10 and additional regulatory factors that suppress autoreactive T cells and promote tissue protection. In MS, B10 cells are often defective, leading to insufficient IL-10-mediated regulation.

Restoring the number and function of these Bregs is thus critical to re-establishing immune balance. This is where helminth infections bring a distinct advantage: they robustly expand and activate these IL-10-producing regulatory B cells, enabling a more effective anti-inflammatory and neuroprotective response than the native system can achieve alone.

How Helminths Restore Immune Balance in MS

Helminths induce a coordinated, multifaceted immune regulatory network that addresses the systemic IL-10 imbalance via multiple mechanisms:

  1. Induction and Expansion of Functional IL-10-Producing Regulatory B Cells
    Helminths stimulate the proliferation of CD19+ Bregs secreting IL-10 along with neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). This dual action suppresses autoimmune inflammation while directly supporting neural repair.
  2. Broad Immune Modulation Through TLR2 Signaling
    Parasite antigens upregulate Toll-like receptor 2 (TLR2) on B cells and dendritic cells, leading to MyD88- and ERK-dependent signaling that suppress pro-inflammatory cytokines (IL-1β, IL-6, IL-12, TNF-α) and simultaneously enhances IL-10 and TGF-β production, promoting immune tolerance.
  3. Sustained Effects Require Persistent Helminth Exposure
    Long-term studies show that continuous helminth infection maintains regulatory immune profiles and clinical stability in MS, with parasite clearance reversing benefits and triggering relapse, indicating the necessity of ongoing helminth-derived signals.
  4. Activation of IL-10-Independent Regulatory Pathways
    Helminths also engage the GAS6–TAM receptor axis (TYRO3, AXL, MERTK), selectively restraining pathogenic Th17 cells, adding a complementary layer of immune regulation independent from IL-10 effects.
  5. Promotion of Trained Immunity and Balanced Regulatory Responses
    The helminth-induced environment favors Th2 polarization, regulatory T cell expansion, immunoregulatory monocytes, and microbiome alterations. This supports durable, systemic immune tolerance that minimizes tissue damage.

Supporting Evidence

  • Regulatory B Cell Function: Helminth-infected MS patients exhibit higher frequencies of IL-10+ regulatory B cells producing neurotrophic factors, enhancing anti-inflammatory and neuroprotective responses.
  • Immune Signaling: Helminth exposure increases TLR2 expression and downstream signaling in immune cells, balancing cytokine profiles toward regulation.
  • Clinical Outcomes: Longitudinal studies correlate persistent helminth infections with reduced MS relapse rates and MRI activity; elimination of infection worsens disease.
  • Additional Regulatory Axes: GAS6–TAM receptor pathways activated by helminths dampen pathogenic Th17 responses independently of IL-10.
  • Trained Immunity: Wide-ranging systemic and microbiome effects further bolster immune tolerance.

Conclusion

Elevated IL-10 levels in MS patients mask a deeper systemic dysfunction involving dysregulated IL-10 production and impaired responsiveness. Helminths re-establish immune homeostasis not by simply increasing IL-10 quantity but by shaping a comprehensive, coordinated immune regulatory network that expands functional IL-10-producing regulatory B cells, activates complementary anti-inflammatory pathways, and fosters neuroprotection.

These insights offer a compelling model of MS immune regulation and a promising foundation for novel helminth-inspired therapeutic approaches.

Further Reading

Citations

  1. Seeking Balance: Potentiation and Inhibition of Multiple Sclerosis – PMC
  2. Under the influence: environmental factors as modulators – Frontiers
  3. Decoding disease burden in multiple sclerosis – ScienceDirect
  4. Dysregulation of IL-10 and IL-12p40 in secondary progressive – PubMed
  5. Immune System Dysregulation in the Progression of Multiple Sclerosis – ScienceDirect
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Why Some People Respond to Helminthic Therapy and Others Do Not

Why Some People Respond to Helminthic Therapy and Others Do Not

1. Type of Condition

Helminths work best in conditions where active immune overreaction drives symptoms (e.g., Crohn’s, ulcerative colitis, MS, asthma).

They are less effective when irreversible damage dominates (e.g., late-stage RA with joint destruction, type 1 diabetes after β-cell loss).

2. Individual Immune Baseline

Helminths expand regulatory T cells and promote anti-inflammatory cytokines (IL-10, TGF-β).

People with high baseline inflammation often feel stronger benefit.

Those whose immune systems are already partly regulated may see less change.

3. Genetics and Immune History

HLA haplotypes and cytokine gene variants affect how the body reacts to helminth antigens.

Early-life exposures (infections, antibiotics, gut microbiome shaping) leave long-term immune “imprints” that influence responsiveness.

4. Microbiome Compatibility

Helminths interact with gut bacteria and metabolites.

People with diverse, resilient microbiomes may integrate helminths more effectively.

Dysbiotic or depleted microbiomes may blunt the therapy’s impact.

5. Species and Dose

Different helminths act differently (Necator americanus, Trichuris suis, Hymenolepis diminuta).

Optimal dose varies tenfold between individuals. Too few = no effect; too many = side effects or intolerance.

6. Time and Consistency

Some notice rapid changes (likely microbiome or neuroimmune shifts).

Full immune recalibration usually takes months to years.

Stopping too early, or inconsistent dosing, reduces the chance of benefit.

7. Age and Disease Stage

Younger people generally respond better — their immune systems are more adaptable.

Older patients may still benefit, but response is slower and less predictable.

Early or mid-stage disease responds better than late-stage, damage-driven illness.

8. Patient Behavior

Desperation can lead to overdosing (“more is better”), which backfires by causing flares, GI upset, or anemia.

Careful, guideline-based dosing improves odds of success.

9. Environmental and Lifestyle Context

Nutrition (iron, vitamin D, fiber), stress, and co-existing conditions all shape outcomes.

Supportive environments help helminths establish a beneficial relationship with the host.

Core Principle: People Aren’t Machines

Even with a ~75% response rate, there will always be non-responders.

Every immune system is unique.

Autoimmune diseases differ in mechanism and stage.

Human biology is adaptive and variable.

A high success rate doesn’t mean universality — it means helminthic therapy fits many people’s biology, but not everyone’s.

References

Response Rate Statistics and Clinical Outcomes:

  • Summers, R. W., Elliott, D. E., Urban, J. F., Thompson, R. A., & Weinstock, J. V. (2005). Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology, 129(1), 286-294.
  • Croese, J., O’Neil, J., Masson, J., Cooke, S., Melrose, W., Pritchard, D., & Speare, R. (2006). A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors. Gut, 55(1), 136-137.
  • Capron, M., et al. (2019). Efficacy of the hookworm-derived protein P28GST for treatment-resistant Crohn’s disease patients. Journal of Crohn’s & Colitis, 13(10), 1280-1290.

Immune System Mechanisms (Tregs and Cytokines):

  • White, M. P. J., McManus, C. M., & Maizels, R. M. (2020). Regulatory T-cells in helminth infection: induction, function and therapeutic potential. Immunology, 160(3), 248-260.
  • Johnston, C. J. C., et al. (2017). A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells. Nature Communications, 8, 1741.
  • Maizels, R. M., & McSorley, H. J. (2016). Regulation of the host immune system by helminth parasites. Journal of Allergy and Clinical Immunology, 138(3), 666-675.

Microbiome Interactions:

  • Brosschot, T. P., & Reynolds, L. A. (2018). The impact of a helminth-modified microbiome on host immunity. Mucosal Immunology, 11(4), 1039-1046.
  • Shute, A., et al. (2021). Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis. Microbiome, 9(1), 186.
  • Li, S., et al. (2023). Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation. npj Biofilms and Microbiomes, 9, 43.
  • Reynolds, L. A., et al. (2015). Commensal-pathogen interactions in the intestinal tract: lactobacilli promote infection with, and are promoted by, helminth parasites. Gut Microbes, 5(4), 522-532.

Genetic and Individual Variability:

  • The influence of genetic and environmental factors and their interactions on immune response to helminth infections. (2022). Frontiers in Immunology, 13, 869900.
  • Ovsyannikova, I. G., et al. (2009). Influence of host genetic variation on rubella-specific T cell cytokine responses following rubella vaccination. Vaccine, 27(25-26), 3349-3358.
  • Dendrou, C. A., Petersen, J., Rossjohn, J., & Fugger, L. (2018). HLA variation and disease. Nature Reviews Immunology, 18(5), 325-339.
  • Bomhof, M. R., et al. (2024). The influence of HLA genetic variation on plasma protein expression. Nature Communications, 15, 6354.

Helminth Species and Dose Response:

  • Parker, W. (2022). Socio-medical studies of individuals self-treating with helminths provide insight into clinical trial design for assessing helminth therapy. Parasites & Vectors, 15(1), 413.
  • Feary, J., et al. (2009). Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study. Clinical and Experimental Allergy, 39(7), 1060-1068.
  • Chapman, P. R., et al. (2021). Vaccination of human participants with attenuated Necator americanus hookworm larvae and human challenge in Australia: a dose-finding study and randomised, placebo-controlled, phase 1 trial. The Lancet Infectious Diseases, 21(12), 1725-1736.
  • Hoogerwerf, M. A., et al. (2019). New insights into the kinetics and variability of egg excretion in controlled human hookworm infections. Journal of Infectious Diseases, 220(6), 1044-1048.

Treatment Duration and Consistency:

  • Lamminpää, K., et al. (2024). Health-promoting worms? Prospects and pitfalls of helminth therapy. BioEssays, 46(9), 2400080.
  • Gazzinelli-Guimaraes, P. H., et al. (2021). Helminth-induced human gastrointestinal dysbiosis: a systematic review and meta-analysis reveals insights into altered taxon diversity and microbial gradient collapse. mBio, 12(3), e00975-21.

Environmental and Lifestyle Factors:

  • Williams, A. R., et al. (2017). A polyphenol-enriched diet and Ascaris suum infection modulate mucosal immune responses and gut microbiota composition in pigs. Veterinary Research, 48(1), 13.
  • Tee, E. S., et al. (2022). Gut microbiome of helminth-infected indigenous Malaysians is context dependent. eLife, 11, e71830.

Meta-analyses and Systematic Reviews:

  • Kumar, S., et al. (2021). Use of helminth therapy for management of ulcerative colitis and Crohn’s disease: a systematic review. Parasitology, 148(12), 1424-1439.
  • Haughton, J., et al. (2015). Human helminth therapy to treat inflammatory disorders- where do we stand? BMC Immunology, 16, 12.
  • Ayelign, B., et al. (2023). The effects of helminth infections on the human gut microbiome: a systematic review and meta-analysis. Frontiers in Microbiomes, 2, 1174034.