Helminths

Recent experimental and clinical evidence suggest that helminthic parasites may be considered as a therapeutic option in IBDs. CD is a result of an inappropriate immune response towards normal gut flora and, probably, helminths down-regulate the host immune response towards bacterial antigens. The high prevalence of CD in industrialised Western regions and the low incidence in developing countries may be related to the different incidence of helminthic infestation. ''IBD hygiene hypothesis'' has been formulated based on induction of the disease by extremely hygienic environments in genetically predisposed subjects. Data from experimental colitis seems to show that helminths reduce inflammation, probably counteracting the Th1-driven immune response [185]. In fact, experimental colitis induced in mice and rats with di- or trinitrobenzene sulfonic acid (DNBS, TNBS), develop a Th1-cytokine-driven colitis that shares features with CD [186,187]. Exposure to Schistosoma mansoni or Trichinella spiralis attenuates DNBS-induced colitis and indicates a protective role of nematode infection in Th1-cell-driven inflammation [188]. The authors suggested the possibility of an immunological distraction with helminths as a novel therapeutic strategy in CD.

Recently, therapy with Trichuris suis eggs in patients suffering from CD has been postulated. The life cycle of T. suis begins with the ingestion of embryonated eggs. Embryonated eggs hatch in the proximal small bowel, delivering larvae that migrate aborally and attach to the mucosa of the distal small bowel and proximal colon. After several weeks, they mature and begin to spread eggs. T. suis ova are capable of colonising a human host for several weeks and are eliminated from the body without any specific therapy (self-limiting infection). In an preliminary study, a single dose of 2,500 live T. suis eggs given orally in patients suffering from active CD induced a clinical response in all patients treated and a clinical remission in the large part of cases [189]. Later, a repeated dose of 2,500 live ova given orally every 3 weeks for 24 weeks induced a clinical response in 80% of patients and a clinical remission in 70% [190]. The positive results of these preliminary open-labelled studies showed that helminth therapy is tolerated and effective in the treatment of CD. Helminths inhibit intestinal inflammation by mechanisms different from current medications, and the efficacy of T. suis therapy supports the hypothesis that helminthic exposure provides protection against CD.

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