A Trio of New Helminth Papers

Three articles were recently published on helminths that are worth sharing with you.  Two studied the immune effects (in rodents) of the species, Hymenolepis diminuta.  (This species is native to rodents and one currently used in helminthic therapy.) The third summarized research into using helminths and helminth-derived products to prevent or cure Type 1 diabetes.  All are extremely complex but I can certainly share the gist and my favorite highlights with you.

Paper 1:  This one looked at the role mast cells play in generating the immune response to the presence of the helminths.[i]  For those of you unfamiliar, mast cells are large immune cells that, when stimulated, “degranulate,” and release many immune substances including histamine.  By looking at the role of these cells in the immune response the researchers hoped to “…potentially uncover novel therapeutic applications [of helminths] against inflammatory, autoimmune and neoplastic [abnormal tissue growth, like cancerous tumors] diseases.”  The scientists used Hymenolepis diminuta for their study because, they are considered the “ideal” model:  “…these tapeworms possess potent immunosuppressive properties during concomitant inflammatory disease states (such as colitis), and are known to cause minimal to no tissue damage within the host…”  They go on to say, as I just mentioned, “Not surprisingly, the immunomodulatory and anti-inflammatory properties of H. diminuta are potentially being exploited in the treatment of gut-associated inflammatory diseases – an area currently known as ‘helminth therapy’ which is currently under active investigation.”

Paper 2:  This paper reports how, what amounts to mushed up Hymenolepis diminuta worms (live worms were removed from mice and put through a process which extracted proteins (antigens) from them) affected the immune system of mice in whom colitis was chemically induced.[ii]  To sum up what was certainly an extremely technical paper into a single sentence:  the HD antigen suppressed this colitis by reducing levels of pro-inflammatory cytokines likes tumor necrosis factor-alpha (TNF) via boosting levels of regulatory (anti-inflammatory) cytokines, including interleukin-10:  “IL-10 is a particularly noteworthy cytokine because it is repeatedly implicated in helminth suppression of diseases, including that by H. diminuta.”  They also conclude that their study highlights the “complexity of host-parasite interactions” but on the bright side, “…helminth-rodent model systems have the potential to reveal novel approaches to the management or cure of auto-immune, auto-inflammatory, and idiopathic conditions such as arthritis, diabetes, and inflammatory bowel disease.”

Paper 3:  This one[iii] summarizes some of the research on helminths’ ability to prevent or treat the autoimmune disease, Type 1 diabetes (T1D), the rate of which is increasing “markedly” in recent decades.  The authors postulate that “Decreased exposure to helminths may be the reason for the increased incidence of TID.”  They point out that less developed countries have far lower rates of the disease, as do highly agriculture societies.  A few highlights:

1. Looking at helminths as a potential source of treatment for T1D makes sense, as they have already been shown to ameliorate or prevent other autoimmune diseases, including, among others, arthritis, Graves’ hyperthyroidism, autoimmune encephalomyelitis and inflammatory bowel diseases.
2. Several helminths (Schistosoma, Filaria, and Heligmosomoides polygyrus) and their byproducts have been successfully tested in T1D. (Unfortunately, none of these are the ones currently being used for helminthic therapy because of untoward side effects.)  But looking at just one as an example, Schistosoma:  this helminth has not only been shown, in animal studies, to prevent the development of T1D, but also Type 2 diabetes.  (T2D has a different mechanism in terms of development but also involves the immune system.)  Within 8 weeks, the immune system of diabetic mice switched to a less inflammatory state (Th1 shifted to Th2, which includes the regulatory cytokines).
3. For those interested in the nitty gritty:  the immune response to the presence of helminths is known to include a “…decrease in IFN-γ and IL-17 and increase in IL-4,Tregs, IL-10, TGF-β, macrophages, dendritic cells(DCs), and natural killer T (NKT) cells…Parasitic helminths regulate the host’s immune system and induce type 2 as well as regulatory immune responses, which may prevent the onset of diabetes.” But as the authors go on to say, “…the protective mechanism of helminths against T1D is complex.”  Ya think?!
4. Finally, two sentences from their conclusion: “Abundant evidence indicates that helminths and their by products can exert immunomodulatory effects that prevent or delay the onset of T1D.”  And last and most certainly, not least, “In the future, helminth derived supplements may be included as part of the modern balanced diet.”

In response to the concept – repeated endlessly in so much of this kind of research – that medical science should be directed toward isolating a singleton product from helminths to make into a pharmaceutical drug, I’ll conclude by quoting Dr. William Parker, of Duke University Medical School (who is one of the leading researchers in the field of helminths and the immune system), and a colleague:   “…because the ecosystem of the human body has evolved with vast complexity, it seems unlikely that pharmaceutical interventions will ever prove successful in effectively treating biome depletion-associated disease.”[iv]  Unfortunately, pharmaceuticals are where the money is – not in natural products that can’t be patented.  As they go on to say:

“Biome reconstitution, in contrast, holds a promise for exposure of all individuals to naturally occurring organisms or selected variants of those organisms in a way that is required for human health. Such exposure must be considered a fundamental human right worthy of government support rather than an option for pharmaceutical development. This dichotomy and the fact that paradigms in science and medicine are slow to change might suggest that biome reconstitution is a dream for the distant future. However, with the heavy burden of disease as a driving force, a ‘tipping point’ might be quickly reached after initial successes of pioneers in the field…”

My personal opinion:  with the rates of autoimmune disease, allergy, autism, etc. continuing to escalate, that tipping point should have happened yesterday.

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 [i] Ryan, NM, Oghuma, S. Role of mast cells in the generation of a T-helper type2 dominated anti-helminthic immune response.  Bioscience Reports. 2019. pii: BSR20181771. doi: 10.1042/BSR20181771

[ii] Reyes, JL, et. al. Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25+ T cells to suppress colitis.  FASEB Journal. 2019. fj201802160R. doi: 10.1096/fj.201802160R

[iii] Tang, CL, Zou, JN, Zhang, RH, Liu, ZM,

[iv] Parker, W, Ollerton, J.  Evolutionary biology and anthropology suggest biome reconsititon as a necessary approach toward dealing with immune disorders.  Evolution, Medicine and Public Health. 2013: 89-103. doi:10.1093/emph/eot008