June 7, 2018

UCalgary researchers make breakthrough in understanding of inflammatory bowel disease

New discovery could lead to 'revolutionary' treatment of Crohn’s disease and ulcerative colitis

Author

Sean Myers, University Relations

Andre Buret says he and his research partner John Wallace are on the path toward a new drug that will help treat inflammatory bowel disease.

Andre Buret says he and partner John Wallace are on the path to a new drug that will help treat IBD.

Riley Brandt, University of Calgary

Living with chronic inflammatory bowel diseases (IBD) such as Crohn’s disease or ulcerative colitis can be agonizing, requiring drastic lifestyle changes and expensive drug treatments. There’s no cure for Crohn’s and only surgery can eliminate ulcerative colitis, but University of Calgary researchers have made a discovery, published this month in the Inflammatory Bowel Diseases journal, that could lead to an effective drug treatment for these diseases — and potentially open up new therapies for a wide range of conditions connected to disruptions in the gut microbiome.

“We are now on the path towards a new drug that will help treat these diseases,” says Dr. Andre Buret, PhD. “For patients with IBD, this is extremely exciting because it may open up revolutionary treatment options.”

Buret’s team, including his research partner Dr. John Wallace, PhD, with the Cumming School of Medicine, have identified a key mechanism underlying the ability of certain intestinal bacteria to contribute to the ulceration and inflammation that is characteristic of Crohn’s disease and ulcerative colitis. Moreover, they’ve discovered that hydrogen sulfide-releasing drugs can reverse these effects, leading to resolution of the inflammation and healing of intestinal ulcers.

The researchers observed that in IBD patients, healthy bacteria had found a way to escape the microbiome film that lines everyone’s intestines and turn virulent by accessing excess iron in the gut. By using a hydrogen sulfide-releasing drug to “mop up” the excess iron, they were able to reverse the process. These laboratory studies were performed using tissues from healthy volunteers and from IBD patients. This novel drug is being developed by the company created from their discoveries, Antibe Therapeutics Inc.

Symptoms can manifest in a variety of ways in IBD patients and current treatments involve a host of anti-inflammatories and steroids which can have serious side effects. Some are also very costly and require intravenous infusions.

“This will be an inexpensive alternative drug, which can be taken orally,” says Buret, a professor in the Department of Biological Sciences and associate vice-president (research).

The next step will be for human trials to test how effective the treatment will be on IBD patients. Buret and Wallace will work with UCalgary’s International Microbiome Centre to further evaluate their findings and move forward on the research.

Buret believes microbiome researchers will be keen to explore new lines of inquiry this research has opened up.

“It’s been shown that the gut microbiome plays a critical role to maintain our overall health,” says Buret. “If there are disruptions in the microbiome, research has shown it can cause a number of disorders, not just in the intestine. It goes beyond the intestine. It’s been implicated in arthritis, brain disorders and obesity.

“More studies still need to be done but it’s really exciting to ask these questions. It has huge potential.”

The lab studies for the new paper were performed by Dr. Jean-Paul Motta, PhD, a postdoctoral fellow sponsored by Eyes High and Alberta Innovates fellowships. The research was supported by grants from Crohn’s Colitis Canada, the Canadian Institutes of Health Research, and the National Science and Engineering Research Council of Canada. 

Andre Buret is a member of the Inflammation Research Network, the Snyder Institute for Chronic Diseases at the Cumming School of Medicine, and the Host-Parasite Interactions Program. John Wallace is an adjunct professor in the Department of Physiology and Pharmacology and an associate member of the Inflammation Research Network at the Cumming School of Medicine.