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Autoimmune Tag

The Hygiene Hypothesis

This article is 100% shellfish free.

Allergies and autoimmune diseases: the tragic, internal conflict of man versus self. Allergies are the result of a hypersensitive immune system attacking a benign outside stimuli, and autoimmune diseases are when that stimulus is of one’s own body. Either way, there is one common factor linking both conditions: the immune system. Why, exactly, is our body acting rashly and lashing out against itself with, at times, fatal flare-ups? The mechanisms that cause the irrational responses are known; however, the reason as to why these mechanisms occur in the first place are still up for debate. An interesting idea is called the hygiene hypothesis, and it puts forth the idea that our obsession with cleanliness could be our downfall.

I’m sure you’ve heard the older generation talk about how, back in their day, kids used to roll around in the mud and get dirty and how everyone is too clean these days. Normally I just smile and nod during these conversations at family gatherings, but there is actually some merit to their points. The hygiene hypothesis posits that our need to be “clean and sterile” is what is leading towards the appearance of allergies and autoimmune diseases in children.

Going through the elementary school system, I vividly remember teachers lecturing us on how we were unable to bring peanut-based products to school any longer for fear that we may cause a fatal anaphylactic reaction in one of the kids of the class. My 10 year old self was pissed, I love peanut-butter. But that little incident would stick with me and make me forever curious about allergies.

Interesting side note: anyone notice how you just don’t meet people with allergies anymore as you age? I know there are tons of children with shellfish/peanut allergies, but what about the adults? Where did they go?

Soil transmitted helminths prevalence. Areas in white are least-to-no-concern.

Soil transmitted helminth prevalence. Areas in white are least-to-no-concern.

 

The hygiene hypothesis is a recent idea, and this makes sense considering that hygienic standards in large cities have only improved in the last few decades (mind you, the rise has been drastic). So, let’s pull up some interesting correlations that give evidence to this hypothesis. Developed  and industrialized countries have worked tirelessly in effort to completely eradicate all parasitic infections from within their borders. This is good (understatement), as there are numerous parasites that would be more than happy to call your intestines home and cause extremely painful and fatal infections. As industrialization proliferates, urbanization takes hold and moves rural families to urban city centres, and this removes childhood exposure to infectious organisms. However, this progress is tainted with the knowledge that over 1 in 5 children in these industrialized countries have an allergenic disease, and epidemiological maps display the information that:

The geographical distribution of allergic and autoimmune diseases is a mirror image of the geographical distribution of various infectious diseases, including HAV, gastrointestinal infections and parasitic infections

That is to say, wherever we have an absence of parasitic infections, we tend to have a prevalence of allergic and autoimmune diseases. This image illustrates the stark contrast in location the of Type 1 Diabetes (T1D) outbreaks and the prevalence of various parasitic infections. Note how North America, western and northern Europe, and Australia (all nations considered “industrialized”) have high incidences of T1D (greater than 8/100,000 per year — and upwards of 36/100,000) while nations generally considered “developing” all have low T1D incidences as well as high parasite infection rates.

img-hygiene-hypothesis

Another image showing the location of (non-specific) autoimmune disorders relative to parasitic infections

Okay, the discrepancy is very blatant — but maybe you’re not convinced yet. Perhaps you think that it’s unfair to compare countries separated by their industrialization level, and that there are likely genetic factors involved in autoimmune disease susceptibility. And to that, I give you the following example.

The first instance of noting the discrepancy in allergies and infections came about with the fall of the Berlin wall in 1989. Dr. Erika von Mutius, an allergy specialist, decided to study the children that were once separated by the wall within the now consolidated country. Of the two halves, East Germany was heavily polluted and far less developed than its counterpart — and as such, Dr. von Mutius hypothesized that the children of the East would exhibit a higher incidence of asthma. She was taken aback when she observed the exact opposite — the children of the more developed West were the ones with significantly higher asthma rates (5.9% versus 3.9%) despite cleaner air and better hygienic standards. Hay fever levels also followed this pattern, and to a more severe extent (8.6% versus 2.7%).

These results are remarkable because the study removes the idea that there are significant genetic differences predisposing the children to allergies. Since the studied individuals were all of German descent and all from the very same country, the only major variable was exposure to infectious agents and overall cleanliness — meaning that environmental exposure was the major determinant of overall health.

A doctor treating a parasitic infection in Ethiopia

These results were replicated in 1973. Dr. Eric Ottesen, an allergy and parasite specialist, travelled to the island of Mauke and treated the locals for a tiny roundworm with the antibiotic diethylcarbamazine. He returned to the island 19 years later to find the wonderful result that the proportion of infected individuals dropped from 35% to 16%. However, in contrast to the decreasing trend of parasite infection was a startling increase in allergies and autoimmune diseases. Less than 3% of the islanders had allergies during Dr. Ottesen’s first visit, but this number rose to 15% by 1992. Hay fever, asthma, and eczema were now commonplace on the remote island; and worst of all, a new problem arose that no one on the island had experienced before: a dangerous allergy to the staple food-item, octopus.

So why is this all happening? What is the reason why autoimmune diseases and allergies are popping up when we remove parasites from one’s body?

It all has to do with how our immune system functions. We have two major pathways in what we call adaptive immunity (the part of the immune system that learns and remembers, and is in contrast to the innate immune system) — the Th1 and Th2 paths. To make it easier to understand, we can relate the two pathways of our adaptive immune system to the logging industry, with one being akin to clear cutting (Th1) and the other to selective logging (Th2).

When we suffer from an allergy, the Th2 pathway is what is to blame. It has become hypersensitive and begins attacking benign outside stimuli, like pollen. Many autoimmune diseases are the result of an overactive Th1 pathway (and at times even an overactive Th2 side, as well) and its hypersensitivity results in the unwarranted attack of one’s own body.

As you can imagine, when we are infected with a parasite, our bodies prepare an immune response. The Th1 pathway is the first to be activated, which is usually shut down by the parasite resulting in the Th2 side taking over. Either way, both sides of our adaptive immune system are functional at some point during the infection.

However, when we remove chance exposure to parasites from the environment, scientists believe (and data corroborates) that we develop an immature adaptive immune system that is willing to attack anything that it comes into contact with, regardless of the actual threat level of that stimulus. This then leads to children and adults developing allergies to nuts, shellfish, and strawberries — and to people essentially becoming “allergic” to their own body. Without a real threat to defend against, our body ends up picking fights with things that it has no business attacking, ultimately hurting itself in the process. And as seen with the natives of Mauke, the development of these conditions can arise decades into life as long as the parasites are removed from their body and the environment.

So, what am I getting at? To be honest, I’m not entirely sure. I guess an easy answer would be “don’t be so clean”, or “go swallow some Schistosome eggs if you want to keep eating peanut-butter” — but is that really the proper stance to take? I doubt it. Instead, I propose that we continue to eradicate tropical diseases from the world, seeing as they are a major source of morbidity and mortality; however, I also suggest that we use parasites to our benefit as a means of combatting horrible autoimmune diseases.

Researchers have known about the strange immune-response-interplay between parasite presence and the absence of allergies for years, and are using the tiny worms to our advantage in order treat many allergenic diseases through a process called helminthic therapy. Crohn’s disease, colitis, asthma, multiple sclerosis, and T1D are all autoimmune diseases that can be treated with exposure to various intestinal worms. So although we are actively looking to rid our bodies of these ugly parasites, it seems as though our relationship with them will not be ending any time soon.

Trichuris: a parasite that is being investigated for its therapeutic properties


References

I’m trying out a new reference style. Instead of having a super long list at the end of each document and little parenthesized numbers within the body, I’ll be hyper-linking my sources within the text body. Just click on the yellow words to go to that given source. I may keep it, I may not — we’ll see.


Image sources

  1. University, D. W., Illinois State. 2009. English: Electron micrograph of an adult male Schistosoma parasite worm. The bar (bottom left) represents a magnification of 500 μm
  2. WHO | Epidemiology. http://www.who.int/intestinal_worms/epidemiology/en/
  3. Hygiene Hypothesis for TSO. http://www.fortressbiotech.com/research-development/hygiene-hypothesis.cfm
  4. Italy, U. A. A. from V. 2010. Nursing student Mahammed-Ziad Ahmed administers de-worming medication, Shinile Woreda, Ethiopia, Oct. 19, 2010
  5. Bremser, D. for J. G. 1831. English: Trichocephalus dispar = Trichuris trichiura

 

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