Helminths as an alternative therapy for intestinal diseases

Abstract

Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity, altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings, such as inflammatory bowel disease (IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies, we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use, but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs, since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease, such as the importance of the specific species of helminths used, appropriate dosing regimens, optimal timing of treatment, the role of host genetics, diet, environment, and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method, especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.

Gut Microbiota beyond Bacteria—Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD

“…Similar findings were published for IBS as well [166,167], thus implying B. hominis is a common constituent of healthy human microbiota exerting a protective role in gastrointestinal diseases [156]. Due to the proposed mutualistic interaction of Blastocystis and its host, some authors even suggested using the protist in a manner similar to that described for some intestinal helminths [168], in order to elicit a beneficial immunomodulatory response in patients with IBD [169]. Additional confirmation that B. hominis could be a commensal microorganism comes from a study in which patients with recurrent Clostridium difficile infections (rCDI) were treated using fecal microbiota transplantation (FMT) [170].…”

Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn’s Disease: A Pilot Study (ACROHNEM)

“…Pioneering clinical trials showed that treatments of helminth eggs or larvae provided some clinical improvement in patients with CD and ulcerative colitis with no AEs [4,14,15]. However, a recent phase 2, randomized, placebo-controlled, multicenter trial that tested Trichuris suis ova (TSO) in patients with active CD showed that TSO efficacy was not significantly superior to placebo [16].…”

“…Both the ES-62 glycoprotein from the filarial nematode, Acanthocheilonema vitae, and the P28 glutathione-S-transferase (P28GST) protein from schistosomes could decrease the inflammatory response (Th1 and Th17) and induce an anti-inflammatory/immuno-regulatory response (Th2/Treg). Those findings led to the concept that well-defined products derived from helminths could be used as anti-inflammatory drugs in place of the entire parasite [4].…”

Treatment with P28GST, a schistosome-derived enzyme, after acute colitis induction in mice: Decrease of intestinal inflammation associated with a down regulation of Th1/Th17 responses

“…In addition, these data showed polarization towards a Th2 profile with a decrease in pro-inflammatory Th1 cytokines. Currently, P28GST is being studied in CD patients in a Phase 2 clinical trial (NCT02281916) [7,33]. In order to know the local effect of P28GST, based on its enzymatic activity, we have explored the anti-inflammatory potential of a local injection of P28GST in the absence of adjuvant.…”