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Worms, Germs, and Dirt: What Can They Teach Us About Allergies and Autoimmune Diseases?

Whipworms in the intestine

Whipworms in the intestine. Click to enlarge.

Humans evolved in an environment where they were exposed to animals, dirt, and a variety of pathogens and parasites. Our immune systems evolved to cope with that environment. Now most of us live in a different environment, with safe drinking water, flush toilets, food inspection, immunizations, and public sanitation. This means that we are far less likely than our ancestors to die of infectious diseases or to harbor intestinal worms. But it seems that the cleaner we get, the more likely we are to suffer from allergies and autoimmune diseases. One hypothesis is that our immune systems evolved to require early challenges by parasites and pathogens in order to develop properly. A hygienic environment fails to give our immune system the exercise it needs, resulting in imbalances and malfunctions.

The hygiene hypothesis was first proposed to explain observations like these:

  • Hay fever and allergies were less common in large families where children were presumably exposed to more infections through their siblings.
  • Polio attack rates were higher in high socioeconomic groups than in lower ones.
  • Allergies and many other diseases were less common in the developing world.

Investigation of these and other phenomena is contributing to a better understanding of the immune system, which is a good thing. At the same time, it has led some people to deliberately infect themselves with intestinal worms in an attempt to cure their allergies and autoimmune diseases, which may not be such a good thing. These treatments are far from ready for prime time, are risky, and they have a high yuck factor. The very idea of deliberately infecting yourself with worms is unpalatable, and finding wiggly live creatures in your stool or passing a 20 foot tapeworm are not generally considered to be pleasant experiences. 

The immune system is an incredibly complicated mesh of many different components that interact with each other. The hygiene controversy focuses on Th1 and Th2. To grossly oversimplify, Th1 responds to intracellular pathogens (bacteria and some viruses) and Th2 responds to multicellular parasites like intestinal worms. They produce different kinds of cytokines, but there is a confusing overlap.   Th1 produces inflammation and Th2 suppresses some of that Th1 inflammation and contributes to a pregnant woman’s ability to tolerate the fetus, but it is also involved in producing allergic reactions. Over-activation of either pathway can cause disease, and either pathway can down-regulate the other.  Th1 and Th2 were originally thought to act like a seesaw where one goes up as the other goes down; but it turned out not to be that simple. An early hypothesis was that allergies resulted from an imbalance between the two, and that allergen exposure could somehow restore a balance. The subject is complicated. The more I try to understand the details, the more my head hurts. I hope my superficial description hasn’t misrepresented the truth too badly.

The business end of a tapeworm

The business end of a hookworm. Click to enlarge.

In his book An Epidemic of Absence: A New Way of Understanding Allergies,  Moises Velasquez-Manoff compiles an impressive array of evolutionary arguments and evidence, everything from epidemiologic studies to personal anecdotes, to support the idea that early exposure to bacteria and parasites would reduce the incidence of allergies and autoimmune diseases, and that exposure after the condition had already developed would reduce symptoms. His book is exhaustive and I found it exhausting to read. It buried me in a mass of repetitious details.

It is an eye-opening book in more ways than one. He describes his own difficult quest to obtain worms to treat himself for his allergies and his alopecia. He has to negotiate with the hookworm underground and travel to Tijuana. He applies the larvae to his forearm and lets them burrow into his skin. Almost immediately, he feels “remarkably crappy.” He gets a headache, a hungover feeling, bloating, cramping, itchy bumps on his arm where the larvae entered, vertigo, cramps, diarrhea. The headaches lingered, but the other symptoms eventually subsided. His skin improved, his hay fever disappeared, and his sinuses were clearer for a while; but then his allergies returned with a vengeance. A stool test showed no whipworms. He assumed they had all died and would have to be replaced with new ones, but he was reluctant to let any more hookworm larvae burrow into his arm and risk experiencing all those unpleasant side effects again. He gave up on the experiment, but later his symptoms cleared again and whipworms showed up again in his stools. It’s far from clear what happened. He likes to think it has something to do with the optimum dose. He says, given his symptoms, that he would never recommend hookworms and would never deliberately administer them to his daughter… unless he was sure that she was destined to develop Crohn’s disease and debilitating allergies. Even then, he couldn’t be confident that the treatment would be effective, and he recognizes that only science can settle the question. He recounts many stories of other people who tried worm therapy and their conflicting results. They tried whipworms, hookworms, and even tapeworms, both from species that infect animals and from those that infect humans. Some people claimed to be cured. Some were improved for a time but symptoms recurred when their worms died and they had to keep infecting themselves with new ones. Some got so sick they had to be de-wormed. Some thought they got results but they also got side effects that they were willing to put up with. As with all testimonials, there is no way to know whether improvements were due to the worms or were coincidental.

Tapeworms

Hookworms in the intestine. Click to enlarge.

Worm therapy is being seriously studied as a treatment for inflammatory bowel disease (Crohn’s disease and ulcerative colitis), celiac disease, and multiple sclerosis. Preliminary results are encouraging, but they are mostly case reports and uncontrolled open label studies.  Carefully controlled studies are needed. It’s complicated; for instance, hookworms appear to reduce the risk of asthma but roundworms increase the risk.

Epigenetics and the environment in the womb come into play. Children born to mothers who were exposed to cowshed microbes were less likely to develop allergies. A double-blind randomized controlled study in Uganda showed that deworming pregnant women reduced the odds of her child developing allergic eczema by 82%. One might have expected that would make the child more susceptible, not less. The effects of bacterial exposure are different from those of parasite exposure. It’s complicated.

How ironic that the anti-vaccine folks are worried that vaccines might “overwhelm” the child’s immune system! Far from being overwhelmed, it appears the child’s immune system is not being exercised enough. It apparently needs more practice responding to microbes and parasites in early life in order to avoid allergies and autoimmune diseases in later life.

In a related development, fecal transplants and probiotics are proving to be effective in treating certain health conditions. We have only recently begun to learn about those other organisms that live in our body and outnumber our own cells by ten to one: our microbiome. Our internal and external ecosystems both affect our health. No man is an island.

Conclusion

Germs, worms, allergies and autoimmune diseases are all part of a complex web. If we come to understand the complexities, it could well lead to new strategies to prevent or treat allergies, diabetes, and a host of other diseases. But I don’t think we want to return to an unhygienic, parasite-laden environment. And I question the wisdom of deliberately infecting oneself with worms at this point in history, given the present state of knowledge. Not only is the evidence far from conclusive, but worms are yucky.

 

 

 

 

 

 

 

Posted in: Book & movie reviews, Epidemiology, Evolution

Leave a Comment (23) ↓

23 thoughts on “Worms, Germs, and Dirt: What Can They Teach Us About Allergies and Autoimmune Diseases?

  1. Alia says:

    And what about growing up in a household with pets? I think there were some studies showing that it might reduce the risk of allergy, which would make sense.

  2. pytra says:

    Good piece. Never thought the “click ton enlarge” could be more ironic.

  3. BillyJoe says:

    Coming from a family of nine, a low socioeconomic group, and a developing nation*, I should live forever.

    *oh, I joke. I come from Australia.

  4. RUN says:

    Wouldn’t having worms also help with weight loss? “Prevent allergies and other autoimmune diseases…..and lose weight at the same time!” I am surprised no one has tried to make themselves some money by promoting worms for weight loss!

    In all seriousness, I would rather just take a vitamin D tab verses experiment with worms to try to avoid some of those conditions!

  5. dani681 says:

    I would love to see a discussion about the history of AAP guidelines for introducing foods to infants and toddlers. I think the recommendation of withholding peanuts has caused a great deal of damage, particularly with food allergies.

    I have a family history of autoimmune diseases, as well as lifelong allergies to the general outdoors. Here’s hoping the Petri dish that is daycare has spared my children.

  6. mousethatroared says:

    I find the hygiene theory fascinating. Although, growing up with four siblings, small house, lots of various pets didn’t seem to stop autoimmune issues in me and my siblings…although maybe it would have been worse or maybe my dad’s chemical warfare on fruit pests and molds invalidate the anti-hygiene benefit.

    Here’s another link on the topic of worms and autoimmune intestinal issues, if anyone is interested.

    http://www.scientificamerican.com/article.cfm?id=helminthic-therapy-mucus

    My impression is that the responsible research being conducted uses parasites that can’t reproduce within humans. That seems like a very sensible approach, to me.

  7. tgobbi says:

    A bit of humor: I once saw a cartoon that showed a doctor telling his patient that the results of his allergy tests indicate that “You may have been intended to live on a different planet!”

  8. DugganSC says:

    Tapeworms may have been marketed as diet pills back in the early 20th century. They also might have had as much tapeworm in them as Homeopathic solutions have anything but water (hey… why don’t the homeopaths start marketing tincture of tapeworm as a weight gain solution?).

    As regards allergic reactions, I told a similar tale to a nurse friend of mine who works overseas and she said that there’s a bit of a balance in that early allergic reactions, while they may reduce the risk of asthma, may also result in insufficient oxygen uptake to the brain at an early age. It’s a possible point, although I’m a bit skeptical.

  9. lizditz says:

    Sigh. Worm therapy for autism has been back in the news. (It’s been part of the biomeddler underground since about 2010, according to this snarky account from Kim Wombles.)

    Back in November 2012, The Scientist posted this:

    A growing body of evidence suggests that in some patients, increased inflammation contributes to autistic behaviors. Now, a Phase I clinical trial is under way to measure the effects of infecting autistic patients with a non-pathogenic parasitic worm. Scientists at Montefiore Medical Center at the Albert Einstein College of Medicine in New York and biotech company Coronado Biosciences will test the hypothesis that treating these patients with Trichuris suis, a non-pathogenic parasitic pig whipworm, will dampen their immune responses and ameliorate repetitive and irritable behaviors.

    “The trial is a novel approach [to autism treatment] with a naturally occurring drug delivery system”—a parasitic worm, said Eric Hollander, a Montefiore psychiatrist and head scientist on the trial.

    link to the listing in Clinical Trials.

    Discussion of worm therapy by PalMD (Peter A. Lipson, behind the white coat).

  10. lizditz says:

    I have a comment in moderation about a clinical trial of worm therapy for autism. Looking back over my records, I see the Wall Street Journal covered this very researcher (Hollander) in “In a Squeaky-Clean World, a Worm Might Help Fight Disease”, published Feb. 14, 2012. In that article, Hollander claimed he would start recruiting in March 2012. Almost a year later, the clinical trial page says “This study is not yet open for participant recruitment.”

    I wonder what is causing the delay.

  11. aabrown1971 says:

    Dr. Hall: I will definitely come back and read this later. Thought you would get a laugh – I just sat down for lunch and was getting ready to read my daily dose of SBM when your lovely graphic came up. :-) I’ll be back.

  12. niftyblogger says:

    So, I know you guys have reviewed these people on here before, but, what you said above in the paragraph discussiong th1 and th2 responses made me wonder….so, why are these people wrong? http://mpkb.org/ and http://www.marshallprotocol.com. They often say everything in your third paragraph.

    Perhaps the problem with them is not always their biology because they use resources and ideas that are not particularly new or original, and draw some interesting (though hasty) conclusions. BUT they DO dangerously propose a treatment that is untested and has not been scrutinized for logical fallacies – of which there are MANY.

    What do you think of the MP? Is it total fiction or is it just hasty action based on some real evidence? If fiction, why specifically?

  13. Janet says:

    Worms aren’t yucky–they’re just…worms. I have a bin of them in my basement and they make short work of my garbage in the winter when the outside compost is frozen (I never seem to get it hot enough to get through the really cold days–although it is a very Northwest-y 65 degrees today!) I am grateful to them and will have a big bin of “worm dirt” for the garden in the spring. If I were starving, I would not hesitate to eat them.

    Having said that, I had pinworms (not sure what they really are) as a child–two or three times. My mother won’t talk about it because she is mortified about such things and doesn’t want to even think about them. We had to take some pills and have our bottoms inspected under a bright light! It was kind of embarrassing even at age six.

    So here’s the anecdote: In spite of this, I am pretty much allergic to most of the animal and plant world–we always had a pet, and though I had only one sibling, I spent loads of time with dozens of cousins and played outside in mud and dirt a lot. My children and grandchildren are also plagued with allergies and autoimmune diseases, although some of this likely comes from the other side of the family in the case of the autoimmune diseases. But perhaps, pin worms just weren’t the right species??

    I read somewhere that there is some criticism of the hygiene hypothesis and was looking for that in the post. I wonder if anyone knows more about that? The fact that something “makes sense” doesn’t cut it, as we all should know by now. Homeopathy “makes sense” to many people when they first hear of it. I’m not saying the hygiene hypothesis is equal to homeopathy, just that there might be problems with it.

  14. Harriet Hall says:

    The hygiene hypothesis has morphed over the years. Basically, “it’s more complicated than that.” The Wikipedia article mentions some alternative hypotheses. http://en.wikipedia.org/wiki/Hygiene_hypothesis#Alternative_hypotheses

  15. NYUDDS says:

    Off-topic, but this is the first I have heard of the Dr. Oz article in the New Yorker Magazine, a 9- page compilation of almost everything Oz including an opinion by David Gorski and others, woven through the account:

    http://www.newyorker.com/reporting/2013/02/04/130204fa_fact_specter?currentPage=9

  16. Anyone that have worked with hygiene hypotheses , either testing rats or analyzing epidemiological data, knows that the time of exposure and genetics factores are crucial. It makes sense on the bell curve, some organisms are prone to th1 while other are more th2. Take for exemple people with natural high dose of IgE

    The data have been shown that the diversity of the bacteria are also essential to induce a “protection” for the selfshoot of the immune system. As you said, this area of research is extremely complex and we a just starting to understanding the role between epigenetic on immunology. Maybe we should understand how our ancestor lived in order to prevent many common diseases of today.

    Our body can cope with our new environment (after industrialization) up to a certain point. I mean that we can buffer some possible not know factor to our genes, but that has limites. Our body is not used to the giant amount of fat and sugar of today as well a super clean environment.

    Maybe if kids just restart to playing with other kids on parks it could be enough… not body knows. I my case the boyscout was a great opportunity to play in the mud and have a real childhood :)

  17. pharmavixen says:

    As a young mum, I embraced the hygiene hypothesis because it gave moral credibility to my half-assed housekeeping. And there was all sorts of anecdotal evidence favouring it all around me. My kids were healthy, while the two obsessive neat freaks on my street (scrubbing the baseboards with bleach, washing the entire ground floor every day etc) had sons who suffered from asthma and serious allergies.

    But yes; it is more complex than that. As well as the fat and sugar and the superclean environment compared with what we evolved in, also we live a lot longer, and thus have a greater chance of developing an autoimmune disorder at some point.

    Harriet, for the “Click to enlarge,” you forgot to add the “MWAAAAAAAAA!”

  18. niftyblogger says:

    Yeah, Harriet, I know Mark Crislip covered the MP there. I read it years ago. You didn’t seem to follow my question. You said word for word some of the same stuff they’ve said and I want to know if you agree or disagree that you may have something in common with the MP and whether or not that affects your case against them.

  19. Harriet Hall says:

    @niftyblogger,

    Everything Mark Crislip said still stands. I agree with his assessment of MP and nothing has changed. I explained how complicated this is and how we don’t have any real answers yet for ANY therapies based on the hygiene hypothesis. Speculations about how any of this might relate to the hypotheses of MP and vitamin D are interesting to wonder about but essentially useless until the hypotheses are tested.

  20. Janet says:

    @HH

    Thank you for the update. I will follow up because I am upset that all the cousins, mud, pets, my mother’s awful housekeeping, and the pinworms did not save me from these awful allergies/allergic asthma, and I don’t want to blame the hygiene hypothesis just because of my own anecdotal issues. :-)

  21. RUN says:

    I am not saying vitamin D is a miracle pill or that there is a direct cause/effect relationship, but there seems to be a lot of research to support that having low levels of vitamin D contributes to autoimmune conditions such as type 1 DM, MS, Lupus, etc. Maybe not as strong research for allergies, but more studies are being done on pregnant women and how their vitamin D level may be impacting their child’s development.

  22. Patrick says:

    Another thought-provoking post. Thanks!

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