Helminths and Inflammatory Bowel Disease: Some Promising News

Exciting news! It’s been ages since I had any good research on the macrobiome to report to you, and this paper is a all kinds of awesome.

To start, the justification for this research: “The increased prevalence of auto-inflammatory conditions, such as diabetes, arthritis, multiple sclerosis, and inflammatory bowel disease (IBD), coupled with a lack of cures for these conditions underscores the need for innovative approaches to manage idiopathic disease.”[i]  The authors go on to point out that the inverse relationship between hosting helminths and developing auto-inflammatory diseases is well established.

“The concept of helminth-therapy to treat idiopathic auto-inflammatory disease is intriguing because it seeks to harness eons of host–parasite co-evolution—that is, the hosts’ natural immune response to infection with a parasitic helminth has the bystander effect of affecting the course of concomitant disease. While seemingly counterintuitive, Desowitz (1980) elegantly presented the concept of the “Harmonious Parasite” and numerous studies with helminth–rodent model systems have shown that deliberate infection with parasitic helminths can reduce inflammation.”

Using a mouse model (for reasons you will understand in a moment), Canadian researchers tested the effects of the helminth Hymenolepis diminuta cysticercoid (HDC) on colitis.  HDC is a kind of tapeworm native to rats:  it’s a mutualist, benefiting its rat host by improving immune status, while the rat provides it comfortable living conditions.  In non-native hosts, it lives only a week or two.  The scientists state that they zeroed in on this organism since it, “…is an intriguing candidate as a ‘therapeutic helminth. Infection is by ingestion and the worm does not migrate through the host; rather, it seeks to establish in the small intestine. Bearing no teeth or hooks, it does no obvious abrasive damage to the host. It is not auto-infective and its life-cycle requires an invertebrate host, so there is no direct person-to-person spread. Natural infection is rare in humans, typically restricted to malnourished or immunocompromised individuals and can treated with antihelminthics.”

The researchers had two questions they wished to answer with this study.  Firstly, what is the window of opportunity to treat colitis with helminths?  Secondly, they wished to see if already existing intestinal inflammation inhibits the host’s ability to eradicate the helminths.

The results:  mice that received the HDC prior to the researchers chemically inducing colitis in the animals showed markedly less disease manifestation.  For example, the HDC-mice had a much smaller drop in body weight, less shortening of the colon, and the average disease score was reduced by 50%.  The HDC-mice, to no one’s surprise, had increased levels of regulatory cytokine production, modulating the inflammatory response, as opposed to the non-HDC-mice, which had reduced levels of regulatory cytokines, including IL-10.

The scientists were also able to establish that adding HDC to a treatment regimen for mice with induced colitis “hastened recovery.”  They point out that there is natural variability in mice’ ability to recover from chemically induced IBD.  The non-HDC-mice, at 11 days after induction, had recovered their body weight, but at 14 days still showed mild signs of disease.  However, the HDC-mice not only recovered their body weight: they also were thriving and were “…not different from control naïve mice at 14 days…” post induction of colitis. What’s really amazing is that even giving mice HDC 3 days after having colitis chemically induced, led them to be indistinguishable from non-treated controls 14 days later.  That is, giving HDC both before and shortly after colitis has been induced led mice return to perfect health in 2 weeks.

The answer to the second question: having the inflammatory bowel disease did not change the mice’ ability to expel the HDC.

So to sum up their findings:

1. By using a helminth not native to a particular animal – in this case a tapeworm native to rats, not mice, so it was rapidly expelled – several days before the induction of colitis, the scientists were able to protect the animals from developing severe disease.
2. In young animals (3 weeks old), giving the helminth earlier (10 days before, but not 8 days before as they did with the adults animals), protected the baby mice. The authors point out that this is important to take under advisement when contemplating a treatment regimen.
3.  For adult animals, giving the HDC provided protection when given only 4 days prior to colitis being induced – but the protection was less so than when the HDC was given 8 days before.  So longer exposure to helminths is more protective…which makes sense.
4. HDC greatly improved recovery times from colitis even if given after the induction of the disease.

A poorly designed study on humans with IBD done years ago was abandoned  half way through because there was no statistically significant differences between the control group and the treated group, who were being given the helminth TSO (Trichuris suis – a whipworm native to pigs)…even though earlier studies had shown excellent results.  Upon the failure of that trial, efforts to research helminthic therapy for treating humans was mostly abandoned.  The authors of this paper point out that the failure of one type of helminth in one study was not enough to give up research.  Thus, they conclude that, “…we suggest it is premature to abandon the potential of helminth therapy and that in-depth analyses of helminth infection in murine models of disease will aid in unraveling the complexity of immunoregulation, with the potential to identify targets for therapeutic intervention in auto-inflammatory disease.”

Let’s hope that their amazing results spur the scientific community to revisit the idea of helminth therapy, as the current array of treatments is completely inadequate, fraught with side effects (see here and here for more on this)  and all too often, ineffective.

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[i] Li, S.; Rajeev, S.;Wang, A.;McKay, D.M. Infection with Hymenolepis diminuta Blocks Colitis and Hastens Recovery While Colitis Has Minimal Impact on Expulsion of

the Cestode from the Mouse Host. Pathogens 2021, 10, 994. https://doi.org/10.3390/pathogens10080994.