Autoimmune disorders arise when an individual’s immune system recognizes self as a foreign entity (such as a bacterium), causing an inappropriate immune reaction that damages healthy cells and tissues. There are over 80 different types of autoimmune disorders including Crohn’s disease, multiple sclerosis, Type 1 diabetes, and for many of these diseases a viable treatment option has not been found.
Dr. Joel Weinstock from Tufts University in Boston has pioneered a novel treatment for gastrointestinal autoimmune disorders such as Crohn’s disease and ulcerative colitis known as helminthic therapy. In simpler terms, Dr. Weinstock treats autoimmune disorders of the gut by encouraging patients to ingest a dose of parasitic worms.
This may seem like a crazy idea, but the logic behind it is sound. The incidence of autoimmune disorders has increased at an alarming rate in the 20th century and the prevalence of autoimmune disorders appears to be highest in the industrialized parts of the world. Advances in sanitation and the introduction of antibiotics have drastically improved the average life span and reduced morbidity due to gastrointestinal infection. Although we all sleep well knowing our countertops are germ-free, it is becoming clear that a few consequences can be attributed as well. As per the hygiene hypothesis, many scientists now believe that lack of exposure to pathogens such as bacteria, viruses, and parasites may actually be a factor in the manifestation of autoimmune disorders plaguing the western world. It has been observed that a higher incidence of parasitic infection corresponds to a lower prevalence of autoimmune disorders and this is observed in less developed (and therefore less ‘sanitized’) environments1. Prior to modern sanitation practices and drug development, infection with parasitic worms was common; in the 1930s and 1940s, 70% of children in the southern United States living in a rural environment were infected by helminths2. The notion that these worms have been living inside us for thousands of years suggests a strong ability to co-evolve with their host; this means that humans have become more adept at handling the presence of these worms and the worms have found new ways to hide from the immune system of the host. Like humans, the worms want a warm, cozy place to live and while exploiting their environment for food and resources, they must avoid killing their host.
To test their hypothesis that the introduction of parasitic worms could reduce the severity of certain autoimmune disorders such as Crohn’s disease and ulcerative colitis, the Weinstock lab treated mice afflicted with irritable bowel disorder (IBD) using doses of Trichuris muris, Heligmosomoides bakeri3, and schistosome eggs4. Treatment with any of these parasites provided protection from the autoimmune disease in the mice, so the trials were moved into humans3,4. Pig whipworms (Trichuris suis) were the parasite of choice, as these helminths normally infect pigs but can live within the human gut for a few months without the risk of entering the bloodstream. After giving 29 patients weekly doses of whipworm eggs, the researchers found that 80% of the patients had decreased symptoms and 72% were actually in remission5. The success of these trials has prompted studies in other autoimmune disorders including multiple sclerosis (MS), autism, and asthma, as well as spurred plans to use this therapy to treat psoriasis, type 1 diabetes, and more1.
The Fleming Lab from University of Wisconsin published data from the first clinical trial involving helminthic therapy for MS in 2011. This autoimmune disorder affects the central nervous system (brain and spinal cord) with a wide variety of neurological symptoms. These researchers found that helminthic therapy showed promise, although future trials will require a larger test number and a prolonged follow-up period. They reported some minor adverse effects on the gut, but overall the study showed that the helminthic treatment causes neither increasing autoimmune reactions nor toxicity from the worms. The excitement surrounding this type of therapy for treatment of MS lies in the idea that a gut parasite can alter actions of the immune system in other parts of the body.
The mechanism underpinning this treatment is immunomodulation by the parasites. It has been shown that the presence of the parasites affects immune regulation, decreasing the activity of the cells that cause the autoimmune reaction. Additionally, studies in mice have revealed that the worms actually shift the bacterial gut population toward organisms typically found in a healthy gut, which is the aim of probiotics1.
Although this therapy has shown great promise in the treatment of a variety of different autoimmune disorders, there are uncertainties. The use of a pig parasite obviously helps avert many of the undesirable effects of infection, but a group at the University of Nottingham, UK has also used Necator americanus, the human hookworm, in a clinical trial for treatment of asthma7. Use of a human parasite could pose the threat of developing serious infections. In addition, there is some postulation that introducing pathogens may actually stimulate a more serious autoimmune reaction by activating the immune system. The ultimate goal with this therapy is to treat patients with the parasites, but to keep the infection under control; in the case of adverse reactions to the parasites, anti-helminth drugs can be introduced.
A number of different research studies report on the efficacy of the treatment with the added benefit of little to no side effects. Various online blogs outlining the experience of helminthic treatment have appeared (a few are listed below), many of which relate the experience of the inoculation and aftermath of the treatment. Some online blogs discuss negative consequences of the treatment, which is absent from many of the published findings, but many also highlight the life changing results experienced post-inoculation and the recurrence of symptoms once they go off the helminthic treatment.
For anybody still feeling squeamish about the idea of ingesting parasites, try to think about it as a probiotic, similar to the yogurt you would find at the grocery store. This type of therapy is a way to control the type of organisms living inside of you, and to choose the ones that will be most beneficial to your health. To read more about helminthic therapy, some informative review papers are listed below, as well as the afore mentioned blogs.
Reviews: Elliott, D.E., Weinstock, J.V. (2012) Where are we on worms? Current opinion in gastroenterology 28(6):551-556.
Hunter, M.M., McKay, D.M. (2004) Review article: helminths as therapeutic agents for inflammatory bowel disease. Ailment Pharmacology Therapy 19(2):167-77.
Fleming, J.O. (2013) Helminth therapy and multiple sclerosis. International Journal for Parasitology [epub ahead of print].
References (1) Weinstock, J.V. The Worm Returns. Nature 491, 183-185 (2012). (2) Weinstock, J. V., Summers, R. & Elliott, D. E. Helminths and Harmony. Gut 53, 7–9 (2004). (3) Elliott,D.E.,Urban,J.F.Jr,Argo,C.K.& Weinstock, J. V. Does the failure to acquire helminthic parasites predispose to Crohn's disease? FASEB J. 14, 1848–1855 (2000). (4). Elliott,D.E.et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am.J.Physiol.284,G385–G391(2003). (5) Summers,R.W.,Elliott,D.E.,Urban,J.F.Jr,Thompson, R. & Weinstock, J. V. Trichuris suis therapy in Crohn’s disease. Gut 54, 87–90 (2005). (6) Flemming, J.O. et al. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Multiple Sclerosis Journal 17(8), 743-754 (2011) (7) Feary, J.R. et al. Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin Exp Allergy. 40(2), 299-306 (2010).
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