Inflammatory Bowel Diseases (IBD) are a group of chronic autoimmune diseases affecting the digestive track, primarily represented by Crohn’s disease and ulcerative colitis. Both types of IBD are caused by an inappropriate immune response in genetically susceptible individuals to intestinal microbial species, however, the site and nature of inflammation differ between the two diseases.
Crohn’s disease can affect the entire intestinal tract from the mouth to the anus, whereas ulcerative colitis mainly affects the colon and the rectum. Although the role of innate cells is pivotal in Crohn’s disease, both conditions are T‐cell‐mediated and characterised by increased levels of interleukin (IL)‐6, IL‐17, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α. However, the immune response in ulcerative colitis appears to be more skewed towards a T‐helper cell type 2 (Th2) response, with increased levels of IL‐4 and IL‐13 production in the tissue.
The current treatments for IBD rely on nonspecific immunosuppressive drugs, such as steroids, antibiotics, and immunomodulators targeting the TNF pathway or the gut‐homing integrin α4β7. However, the repetitive cycles of acute inflammation followed by temporary remission in IBD result over time in severe impairment of gut function, motility and tissue remodelling.
Although there are several medications on the market for IBD, they generally only provide temporary relief and it is still expected that 70% of patients with Crohn’s disease and 20-30% of patents with ulcerative colitis will require surgical intervention. There is an unmet medical need to develop new therapeutics for IBD that are more effective with longer-term benefits.
QIMR Berghofer leads promising new avenues of research with the understanding of the pivotal role the mucosa, the microbiome and microbiome-derived metabolites play in the development of the diseases.
One other avenue utilises helminth-derived therapeutics to treat autoimmune diseases, such as IBD and coeliac disease. Nematodes, and hookworms in particular, have been shown to ameliorate chronic inflammatory diseases by promoting immune regulation, particularly the induction of regulatory T cells and the modification of the intestinal microbiota.