Helminths and Colitis: Friends or Foes?

Abstract

The mechanisms by which gastrointestinal helminths can modulate inflammatory disorders are of great scientific interest for the development of novel therapeutics to treat disease. Currently, the established literature emphasizes the protective role of helminth infection in murine models of inflammatory bowel disease (IBD). Using the gastrointestinal helminth Heligmosomoides polygyrus (H.polygyrus), we demonstrate that helminth infection exacerbates IBD in 2 different models - induced with oxazolone or dextran sulfate sodium (DSS). Helminth exacerbation of DSS colitis is dependent on host gender, host specific pathogen free (SPF) status and the dose of H.polygyrus infective larvae but is independent of the phase of H.polygyrus infection. Helminth exacerbation of disease is associated with increased inflammation in the colon as well as increased systemic inflammation, including splenomegaly and neutrophilia. This heightened systemic inflammation is characterised by significant bacterial translocation to the spleen, significant shifts in bacterial composition and a loss in intestinal epithelial integrity, following helminth infection. Administration of probiotics during helminth infection reduces helminth exacerbation of DSS colitis, restores epithelial integrity, significantly reduces bacterial translocation to the spleen and ameliorates splenomegaly. Our work uncovers an unexpected and novel role for live helminth infection in exacerbating IBD and suggests that helminth-induced dysbiosis of the microbiota may drive disease. These studies reveal restoration of the microbiota through probiotics as a potential therapy for the treatment of gastrointestinal inflammatory disorders