Trichuris suis therapy in Crohn's disease

James A Clifton Center for Digestive Diseases, Department of Internal Medicine, University of Iowa Roy J and Lucille A Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Gut (Impact Factor: 14.66). 01/2005; 54(1):87-90. DOI: 10.1136/gut.2004.041749
Source: PubMed


Crohn's disease is common in highly industrialised Western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Thus exposure to helminths may help prevent or even ameliorate Crohn's disease.
The aim of the study was to determine the safety and possible efficacy of the intestinal helminth Trichuris suis in the treatment of patients with active Crohn's disease.
Twenty nine patients with active Crohn's disease, defined by a Crohn's disease activity index (CDAI) > or =220 were enrolled in this open label study.
All patients ingested 2500 live T suis ova every three weeks for 24 weeks, and disease activity was monitored by CDAI. Remission was defined as a decrease in CDAI to less than 150 while a response was defined as a decrease in CDAI of greater than 100.
At week 24, 23 patients (79.3%) responded (decrease in CDAI >100 points or CDAI <150) and 21/29 (72.4%) remitted (CDAI <150). Mean CDAI of responders decreased 177.1 points below baseline. Analysis at week 12 yielded similar results. There were no adverse events.
This new therapy may offer a unique, safe, and efficacious alternative for Crohn's disease management. These findings also support the premise that natural exposure to helminths such as T suis affords protection from immunological diseases like Crohn's disease.

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Available from: Robert W. Summers, Jan 23, 2014
    • "In human populations, the ―hygiene hypothesis‖ suggests that diminished pathogen/parasite exposure, often due to urbanization, has led to a steep increase in the frequency of allergies and autoimmune diseases such as Type 1 diabetes and multiple sclerosis (Yazdanbakhsh et al. 2002). Therapies for autoimmune diseases using helminths are currently being developed, such as using whipworm (Trichuris suis) to downregulate the patient's immune response and achieve remission in Crohn's disease (Summers et al. 2005). The immunoregulatory role of parasites is especially important in multi-species systems, where high parasite biodiversity is shown to have a dilution effect on chronic infections. "
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    Conservation Biology 09/2015; DOI:10.1111/cobi.12634 · 4.17 Impact Factor
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    • "The strains of TSO currently available (one company) is the strain used by Weinstock in clinical trials reported in 2005 [16] [18], originally obtained in collaboration with the United States Department of Agriculture. The strains of NA (three companies) and TTO (two companies) currently in use were acquired by individuals when traveling in areas where the organisms are endemic. "

    01/2015; 3:1-22. DOI:10.4303/jem/235910
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    • "Although T. suis is a pig whipworm, it has been shown to shortly colonize the human intestine, without inducing any adverse symptoms (Beer, 1976). Oral administration of T. suis eggs has given promising results in initial small clinical trials inducing disease remission in patients suffering from Crohn's disease, ulcerative colitis, and multiple sclerosis (Summers et al., 2005a,b; Fleming et al., 2011). The effectiveness of T. suis administration in diminishing symptoms of such inflammatory diseases can be explained by the type of immune response that is induced by this helminth. "
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    ABSTRACT: The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.
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