IBD study aims to end misery for millions
Is gut microbiome the key to why immune system goes haywire?
With three brothers affected by either Crohn’s disease or ulcerative colitis, Kathleen Crispi knows she’s at high risk for one of the literally gut-wrenching conditions known to run in families. About a year ago, she volunteered to take part in the largest-ever study of inflammatory bowel disease (IBD) — research that hopes to unlock the cause of Crohn’s, with the ultimate goal of finding cures for both major forms of the condition.
The Canadian-led, international Genetic, Environmental, Microbial (GEM) project has just reached its target enrolment of 5,000 participants around the world, all unaffected children or siblings of people with Crohn’s.
“Even getting to a stage of having biological markers or being able to identify people who are likely to develop the disease ... would be a really big win out of this study,” said Crispi of Guelph, who has two brothers with ulcerative colitis and one with Crohn’s. “Obviously, we know it runs in families,” said Crispi, 32. “I have two young children and I have two nephews and a niece, as well, so for us anything that would lead to earlier detection would be fantastic. “But, of course, a cure would be amazing.”
Crohn’s and ulcerative colitis are autoimmune diseases which cause inflammation of the lining of the gastrointestinal tract, disrupting the body’s ability to digest food, absorb nutrition and properly eliminate waste. Symptoms include abdominal pain, cramping, gas, bloating, fatigue and diarrhea. With Crohn’s, inflammation can occur anywhere in the GI tract but is usually in the lower part of the small intestine and the colon, or large bowel. Ulcerative colitis affects only the colon, including the rectum and anus.
About 250,000 Canadians have IBD, which affects an estimated 10 million people worldwide. And its incidence is on the rise, said Mina Mawani, president and CEO of Crohn’s and Colitis Canada. “These people have unbelievable pain, they have bloody diarrhea, they could be going to the bathroom up to 20 times a day,” said Mawani. “People feel that there’s a lot of stigma associated with a bathroom disease, so they don’t speak about it very often. “But if you have to go to the washroom 20 times a day ... you may not want to go to events, you may not be able to hold down a job. It really is a socially isolating disease.” Medications and in some cases surgery to remove chronically inflamed portions of the intestines can help keep IBD under control in 50 to 60 per cent of cases, “but we still haven’t cured anyone,” said Dr. Ken Croitoru, principal investigator of the GEM study. Researchers are tracking subjects’ diet, immune function and changes in their intestinal microbiome, as well as trying to decode any genetic anomalies and potential environmental factors that may end up sparking the disease. Since 2008, when the study began, 70 participants have gone on to develop Crohn’s, while 15 have been diagnosed with ulcerative colitis, said Croitoru, a gastroenterologist at the Mount Sinai Inflammatory Bowel Disease Centre in Toronto. “That gives us the opportunity to go back and say ‘OK, what was there when they were healthy that distinguishes those 70 from the rest of the crowd?’ ” he said. Researchers are paying particular attention to each person’s gut microbiome, the natural bacterial community inhabiting the gastrointestinal tract.
“There’s something there that seems to be important in triggering the disease,” said Croitoru, speculating that some as-yet-unknown factor may alter the microbiome. “We think there’s something that’s changed the microbiome that has affected the way the immune response works, and instead of having a normal relationship like most people have, the immune response goes haywire.
“The idea is that to understand how that changes, you have to look at it before the disease can set in, before everything is so bad and the fire’s raging so you can’t tell where the fire started.”