Helminthic Therapy: A Review of the Current Status of Research

A couple of weeks ago, I found an interesting article in The Scientist that does a great job of summarizing the current status of helminth research.[i]  I have been too busy in my “real” life to read it though, until this past weekend. So, for your reading pleasure…here goes.

The author of the article interviewed many of the main figures involved in the field. He starts with researcher, Alex Loukas, at James Cook University in Australia –  where some of the best helminth studies are going on – who has inoculated himself with Necator americanus (hookworm).  Why you ask?  Because,  “…work by his group and others indicates that there could be some unique benefits to controlled, low-level infection with certain worm species, particularly for combating so-called Western diseases, including allergies, autoimmune disorders, and various other inflammation-related conditions.”

Here are my top 10 highlights for you:

1.  Rick Maizels, another renowned helminth research, points out that we co-evolved with helminths, and that until 100 or so years ago, all people had them.  He is studying the mechanisms by which helminths reduce inflammation:  “Maizels and others have also reported that helminth infection is associated with increased production of immunoglobulin G4 (IgG4), an antibody released by B cells that is associated with anti-inflammatory pathways. Levels of IgG4 typically fall in people whose helminth infections are eliminated with deworming drugs.”

2.  The article covers P’ng Loke’s well-known case study of a man who ingested Trichuris trichuria (human whip worm) eggs to treat his ulcerative colitis.  Loke, formerly of New York University, now at the National Institute of Allergy and Infectious disease, found that the helminths induced the production of IL-22, which led to reparation of the mucosal barrier in the man’s intestines.

3.  Last year, a randomized trial of  hookworm in the UK, for those with relapsing remitting multiple sclerosis (RRMS) found that those infected had higher levels anti-inflammatory Treg cells, and therefore, had few relapses than those in the placebo group.  This is not the first time that helminths have been shown to help modulated MS.

4.  This same London group is doing animal studies, looking at whether or not helminths can protect against diabetes: “had higher levels of anti-inflammatory cytokines such as IL-4 than uninfected controls and were protected from diabetes-like pathology. Loukas and colleagues are now running a randomized controlled trial to assess safety and tolerability of hookworm infection in people who are obese and show insulin resistance or other symptoms of metabolic syndrome.”

5. There has been wide-variety in the success of clinical trials using helminths. Why?  Loke points out that firstly, the placebo effect tends to be strong in the trials and secondly, there is tremendous variability in how individuals respond.  Our immune systems and our individual biomes are so radically different that giving the same dose or same helminth to everyone and looking for a consistent response is a recipe for failure:  “One way to resolve this puzzle could be to learn more about variation in immune system responses to helminths, something that Loke is working on now.”

6.  The article discusses in some detail how scientists are attempting to use secretions from helminths to make pharmaceutical options available. Since these medications are far in the future, I won’t bother to describe them here.  I suggest though that those of you following helminth researchers take a look at the article:  it is very interesting.  One note though:  in 2019, a helminth-derived “medicinal” product was shown to, in mice, lower the risk of developing Crohn’s disease in animals genetically prone.  How?  It seems that it “…promoted growth of certain Clostridiales bacteria that produce butyrate, a metabolite previously shown to promote bone formation and prevent bone loss in mice.”  Which brings me to my next topic…

7.   Some researchers are focusing their work on the interactions between helminths and the bacterial microbiome. This is an unbelievably complex topic.  On really interesting example:  “In one study, for example, Harris, Maizels, and colleagues reported that mice that were inoculated with polygyrus before being infected with a respiratory virus typically showed less lung inflammation than helminth-negative mice given the same virus, but this protective effect disappeared when the experiments were repeated with germ-free mice.”

8.  We know already that the presence of helminths changes the composition of the gut bacteria. I discussed this in this post from X: Loke “…found that infection with Trichuris species was linked to greater phylogenetic diversity of bacteria in the gut.”

9.  Worms appear to manipulate the gut bacteria by fostering the growth of particular species: “for example, Loke and colleagues reported that mice that were genetically susceptible to developing Crohn’s disease had a lower risk of developing intestinal inflammation if they were infected with Trichuris muris, and that this protective effect occurred via the microbiota: helminth infection favored growth of bacteria in the Clostridiales order, which in turn kept a check on the inflammatory bacterial species Bacteroides vulgatus.”  There are multiple other interesting pieces of information in this article, if this topic interests you.

10.  One other interesting point: Loukas points out that helminths affect brain chemistry.  For example, scientists have found, in rodent studies, that helminths affect serotonin levels which would possibly explain, I would imagine, what helminth users call “the helminth high” when first starting self-inoculation.  Says Dr. Loukas:  “It could well be that worms manipulate brain chemistry to make people . . . have a greater sense of well-being than an uninfected person…”

There are WAY more questions than answers still, when it comes to helminths, their effects on the human immune system and the other residents of our biomes. I find it incredibly uplifting  though to read articles like this one because honestly, I do believe that someday helminths will be a major source of relief for so many of us who  currently suffer inflammatory illnesses.

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[i] https://www.the-scientist.com/features/return-of-the-worms-69427