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The therapeutic power of a parasite

Research getting to the guts of Coeliac Disease

Investigators: Dr. Paul Giacomin (James Cook Uni), Dr. John Croese (Prince Charles Hospital), A/Professor Graham Radford-Smith (Royal Brisbane and Women’s Hospital), Professor Nathan Subramanian (QUT), Professor Tony Rahman (Prince Charles Hospital, Distinguished Professor Alex Loukas (James Cook University)

Researchers are examining whether harbouring some parasites in the gut may hold answers to painful health issues such as coeliac disease.

In a recent clinical trial, a research team led by scientists from the Australian Institute of Tropical Health and Medicine at James Cook University (JCU), and clinicians at The Prince Charles Hospital, Brisbane, investigated the potential of “immune-modulating” worms to restore gluten tolerance in patients with coeliac disease.

Immunologist Dr Paul Giacomin, who led the study at JCU, said helminth parasites such as hookworms have co-evolved and adapted to their human host, such that infections in well-nourished people are safe and well tolerated.

Dr Giacomin said hookworms can induce changes in the immune system that can activate or suppress its function, which helps the parasite survive and may have an unexpected collateral effect on other, unrelated inflammatory conditions of the host.

“We know coeliac disease is an autoimmune disorder where an immune response arises in the intestine after gluten consumption, and we are furthering some studies which have suggested hookworm infection in the small intestine, may restore gluten tolerance,” he said. “We undertook a randomised, placebo-controlled trial of hookworm infection in 54 people with coeliac disease, and there was some compelling evidence that emerged. “While hookworms were not able to “cure” coeliac disease and let people return to a normal diet containing moderate levels of gluten, we did observe that people treated with hookworms tended to display improved tolerance to lower gluten challenges, and had reduced gastrointestinal symptoms.”

This fascinating finding has now resulted in the research team being awarded a Coeliac Australia Exploratory Grant to further their research into the potential benefits of gut-dwelling hookworms – with a focus on how these worms may change the gut environment to prevent coeliac disease reactivation after exposure to low levels of gluten.

Senior gastroenterologist at The Prince Charles Hospital Dr Tony Rahman said “This research may have profound implications for the health and lifestyle flexibility or people with coeliac disease, who normally have to adhere to a strict gluten-free diet to avoid accidental gluten exposure.”

The team will now use this Coeliac Australia grant to undertake a series of advanced laboratory analyses – focusing on the gut reactions.

The researchers believe the advanced analyses will reveal the biological reasons of why some people who were treated with the hookworms were able to develop remarkable tolerance to the gluten challenge, while others did not.

Their hypothesis is that hookworms are likely to create an anti-inflammatory environment in the gut, as well as beneficial changes in the balance of healthy and unhealthy microbes in the gut, which together favours the development of improved gluten tolerance in coeliac disease.

 The team hopes that greater understanding of the biological mechanisms that lead to improved gluten tolerance, will advance the development of new treatments such as immunomodulatory therapies, or probiotics for people with coeliac disease, that may not require being infected with live hookworms.

Dr Paul Giacomin is leading the research from the Australian Institute of Tropical Health and Medicine at James Cook University, with clinical gastroenterologists Dr John Croese and Tony Rahman of The Prince Charles Hospital Brisbane, Dr Graham Radford-Smith of the QIMR-Berghofer Medical Research Institute, senior scientists Professor Nathan Subramanian of Queensland University of Technology, and Prof Alex Loukas also of the Australian Institute of Tropical Health and Medicine at JCU.

You can read more about this research here in the journal of Clinical and Translational Gastroenterology.