Helminths and the Hygiene Hypothesis

By Isabelle Guerra

What is it?

The hygiene hypothesis was first introduced in the 1980s by David Strachan. Simply put, the hygiene hypothesis states that early exposure to microorganisms helps contribute to the development of the immune system (Strachan,1989). This hypothesis was an attempt to explain the rising occurrences of autoimmune diseases. An autoimmune condition occurs when immune system activity starts to produce to damage to its own body cells (Fleming, 2013). These diseases include allergies, rheumatoid arthritis, Type 1 Diabetes, and many more. The incidence of autoimmune diseases has been rising and the occurrence of most infectious diseases has declined. Without early exposure to microorganisms it is thought that humans will have a less developed immune response, resulting in the development of inflammatory conditions.

This hypothesis attempts to explain why there is an odd distribution of autoimmune diseases in the world. Many studies include maps displaying a distribution of autoimmune disease that appear to be only in “developed” countries, contrasted with parasite infections in “under-developed” countries. A lot of data supports this explanation, but the mechanisms are unknown.

    

Why is it controversial?

A main pillar of this hypothesis is based on claims that helminth infections have been eradicated in developed countries. Another claim is that allergic diseases are not as prevalent in under-developed countries compared to helminth infections. A study conducted with children in Ecuador found that while 25 percent had at least one documented helminth infection 28 percent had a wheeze, 15 percent had skin test reactivity to an allergen, and 17 percent had eczema (Briggs, 2016). This study attempted to show that while helminth infections were common, so were allergies and allergic conditions.  

Many helminth species have effects on their host that actually promote inflammatory disease. Infection with the helminths Ascaris lumbricoides, Toxoplasma canis, and Toxoplasma cati actually makes patients at a greater risk for developing asthma or Loeffler’s pneumonia. Loeffler’s pneumonia is characterized by white blood cell- rich alveoli and interstitial spaces. White blood cells are indicative of helminth infection.

Therapeutic tapeworms?

The term “helminth” is a broad term used to describe a parasitic worm, fluke, nematode, or tapeworm. Helminths have been a part of human evolution for a very long time. They are able to infect humans successfully through their suppression of immune responses.

     In the human body, Helminths typically trigger an elevated white blood cell count as well as a cellular immune response that favors extracellular parasites (TH2). In an attempt to avoid detection, helminths may secrete proteins that actually favor a TH1 response, which is typically more effective against bacteria and viruses.

     Helminths have been used as a treatment for inflammatory diseases. This is the intentional infection with specific intestinal helminths to try to alleviate some symptoms of diseases (Loker, 2015). Since they typically effect the kind of immune response that is also impacted by an autoimmune condition, they are of great interest for therapeutic applications. The most studied application is the introduction of helminths or their eggs to the human intestinal tract (Zwiernik, 2019). This application has been useful in the treatment of Crohn’s disease. The inflammatory response of Crohn’s disease is due to the immune system attacking the normal biome of the gut. Long term treatment with Trichuris suis led to the patients being at levels of Crohn’s disease activity that would be considered remission.

Summary:

     Autoimmune diseases are on the rise around the world. The Hygiene hypothesis attempts to provide an explanation for this increase by theorizing that less exposure to microorganisms leads to a higher prevalence of autoimmune diseases. This hypothesis has been widely studied, but the underlying mechanisms it is referring to is unclear. It has since been replaced with the “old friends” hypothesis, which is based on the idea that infectious organisms have coevolved with hosts and have genes that are important to the development of the host immune system.

Helminths have coevolved with humans and are adapted to suppressing and modifying our immune response for their survival. This mechanism makes them a valuable potential treatment against autoimmune diseases. Promising clinical studies exist, but there is a large field with room for development.

References:

Briggs, Neima, et al. “The Hygiene Hypothesis and Its Inconvenient Truths about Helminth Infections.” PLoS Neglected Tropical Diseases, Public Library of Science, 15 Sept. 2016.

Fleming, J.O. “Helminth Therapy and Multiple Sclerosis.” International Journal for Parasitology, Pergamon, 5 Jan. 2013,

Loker, Eric S., and Bruce V. Hofkin. Parasitology: a Conceptual Approach. Garland Science, 2015.

Strachan, D P. “Hay Fever, Hygiene, and Household Size.” BMJ (Clinical Research Ed.), U.S. National Library of Medicine, 18 Nov. 1989.

Zwiernik, Jacek et al. “Therapeutic applicability of helminths in autoimmune diseases - literature overview.” Przeglad gastroenterologiczny vol. 14,3 (2019): 168-172. doi:10.5114/pg.2019.88164