Lupus and Helminths: Preventive Promise?

I continue to monitor the macrobiome space, watching as the evidence (very) slowly but surely continues to mount in support of helminths’ ability to alleviate, or even prevent, the development of autoimmune diseases.  The latest news is that, in an animal model, Japanese researchers have found that a species of helminth (intestinal worms native to all mammals), Hymenolepis microstoma (HM), a species of tapeworm, native to rodents,  can stop lupus in its tracks.[i]

First, a little about lupus, in case you’re not familiar.  According to the Mayo Clinic, it is a systemic autoimmune disease that can affect many systems including your joints, skin, kidneys, blood cells, brain, heart and lungs.[ii]  The National Center on Lupus states on their website that at least 1.5 million Americans have the disease, 90% of whom are women.  It is potentially an extremely serious disease:  it is among the top 20 leading causes of death in females, aged 5-64.[iii]

As is the case with all autoimmune diseases, no one knows either the cause or the cure for lupus, and like many others, is treated with an array of immune-suppressants and biological agents.

I have described the known immune-modulatory effect of helminths many times on this blog (2 quick examples of many here and here), so won’t go into details in this post.  For those unfamiliar, a very brief explanation:  in order to survive, helminths have evolved to modulate the inflammatory response of their hosts to keep from being killed off.  They are potent activators of the regulatory system (the off switch to the inflammatory one).  Improved sanitation (toilets, shoes, purified drinking water, etc.) has led to the eradication of  our native macrobiomes in the industrialized world, leaving us with lower levels of regulatory cytokines and thus, the tendency to have excessive and perpetual inflammation.

While many studies now exist in animal models, and some in humans, showing helminths’ benefits in treating diseases like allergy, multiple sclerosis,  and even autism, etc., prior to this paper, none really existed looking at their efficacy in treating lupus.  Apparently, this is because of a lack of a good animal model of the disease.  In this experiment, the researchers used mice that have been bred to spontaneously develop a lupus-like syndrome.

Three different helminths were tested in germ-free mice: Trichuris muris (a roundworm native to rodents); Heligmosomoides polygyrous (another roundworm native to rodents); and Hymenolepis microstoma, which, as I mentioned above, is a different kind of helminth  –  a flatworm (tapeworm).  Only the tapeworm was able to successfully colonize the lupus-prone mice, and thus, it was the only one which ended up being used for this experiment.

The lupus-prone mice, after colonization, were monitored via blood draws, looking for the production of autoantibodies.  Uninfected mice gradually began to produce the autoantibodies, peaking at 8-9 months of age.  However, the mice with the helminths on board never produced autoantibodies.

The kidneys are primary targets for lupus autoantibodies, and the degree of damage can be measured by protein in the urine (proteninuria).  The uninfected mice developed proteninuria around 9 months of age; the  mice with the helminths never developed it.  The mice were autopsied and indeed, in the mice with the helminths, the kidneys were completely normal as opposed to those of the uninfected mice, which showed major pathology.

An interesting note:  if the mice were given an anti-helminth agent after only a month of infection, these protective effects were not seen.  It is the long-term presence of the helminths which provided protection from the development of lupus.

The authors conclude, “Helminthic infections are known to induce immune regulatory cells to modulate immunity.  We found that perivascular inflammatory responses…were suppressed, suggesting that the immune suppression induced in Hm-infected mice attenuates inflammation through activation of regulatory T cells (Tregs).”  This is exactly what so many other studies have found.

This study is significant in that,  “…the suppressive effects of Hm on inflammatory diseases have never been reported. Thus, our report includes two novel findings: the suppression of the natural onset of SLE in a helminthic infection, and the protective ability of Hm against inflammatory diseases.”  The Hymenolepis family of tapeworms are not well-studied in terms of their inflammation suppressing effects in diseases. (It is not completely unstudied though.  I talked about a couple of new papers looking at Hymenolepis dimimuta about a year ago, here.   This paper is a big step forward in providing among the first such studies on these helminths. And lupus is, as I mentioned above, way understudied in terms of helminths.

To end on a really interesting final note:

“Infection with Hm improved all symptoms and signs of SLE and prevented death.”

That is, 70% of the mice with helminths lived until the end of the experimental period, far longer than those uninfected:  “Hm prevents natural development of SLE and prolonged survival of NZBWF1 mice.”

So there you have it.  Yet another feather in the cap for our macrobiotic old friends.

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[i] Olia, A, Shimokawa, C, Imai, T, Kazutomo, S, Hisaeda, H. Suppresion of systemic lupus erythematosus in NZBWFI mice infected with Hymenolepis microstoma.  Parasitology International.  2020. https://doi.org/10.1016/j.parint.2020.102057

[ii] https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789

[iii] https://www.lupus.org/resources/lupus-facts-and-statistics