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
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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.
    Molecular Immunology 07/2014; 60(1):1–7. DOI:10.1016/j.molimm.2014.03.003 · 2.97 Impact Factor
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    • "As a result, helminths and their products are being investigated as potential therapies for inflammatory bowel diseases (IBDs). Several trials of T. suis treatment have been carried out for IBDs in humans (Summers et al. 2005a, b) which have shown positive results. The hookworm N. americanus has also been tested as a therapy for IBDs (Croese et al. 2006; Feary et al. 2010; Daveson et al. 2011) and has been separately shown to alter the gut microbiota in Syrian hamsters (Wang et al. 2009). "
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    ABSTRACT: SUMMARY Human gastrointestinal bacteria often share their environment with parasitic worms, allowing physical and physiological interaction between the two groups. Such associations have the potential to affect host health as well as the bacterial and helminth populations. Although still in its early stages, research on the interaction between the microbiome and parasitic helminths in humans offers the potential to improve health by manipulating the microbiome. Previously, supplementation with various nutritional compounds has been found to increase the abundance of potentially beneficial gut commensal bacteria. Thus, nutritional microbiome manipulation to produce an environment which may decrease malnutrition associated with helminth infection and/or aid host recovery from disease is conceivable. This review discusses the influence of the gut microbiota and helminths on host nutrition and immunity and the subsequent effects on the human host's overall health. It also discusses changes occurring in the microbiota upon helminth infections and the underlying mechanisms leading to these changes. There are still significant knowledge gaps which need to be filled before meaningful progress can be made in translating knowledge from studying the human gut microbiome into therapeutic strategies. Ultimately this review aims to discuss our current knowledge as well as highlight areas requiring further investigation.
    Parasitology 06/2014; 141(10):1-17. DOI:10.1017/S0031182014000699 · 2.56 Impact Factor
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    • "Helminth parasites exert immune-modulatory effects in their hosts that prevent and/or attenuate auto-inflammatory diseases, such as multiple sclerosis, Crohn's disease and T1D [7]–[9]. The induction of Tregs and the associated secretion of IL-10 and TGFβ are events central to the immune responses induced during helminth infection and are also believed to be the principal mechanisms by which helminth parasites modulate autoimmune responses [11], [18], [34], [36]. "
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    ABSTRACT: Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFβ and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro, FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment.
    PLoS ONE 01/2014; 9(1):e86289. DOI:10.1371/journal.pone.0086289 · 3.23 Impact Factor
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