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Researchers Improve Understanding of Inflammatory Bowel Diseases

Inflammatory Bowel Disease (IBD) is a painful condition that causes inflammation and ulcers in the intestine and colon. IBD affects 1 in 150 or over 200,000 Canadians, often with onset in childhood and adolescence. The causes are unknown, but current thinking suggests it is due to an abnormal immune response to environmental factors such as bacteria in the gut and is, at least partly, genetically determined.

Clinician-scientist Dr. Ken Croitoru is the lead investigator of The Gem Project, a prospective study of healthy people genetically at risk of developing Crohn’s disease.

Clinician-scientist Dr. Ken Croitoru is the lead investigator of The Gem Project, a prospective study of healthy people genetically at risk of developing Crohn’s disease.

Bacteria, viruses and fungi in our bodies together comprise what is known as the ‘microbiome.’ This population of microbes number over a trillion per person, and are critical to our health. Understanding how changes in the microbiome impact the development of disease has become a hot area of medical research recently.

Last month, the Canadian Institutes of Health Research (CIHR) and several partners including the Crohn’s and Colitis Foundation of Canada (CCFC) announced a $16-million investment into the Human Microbiome Initiative for seven projects across Canada. The goal is to understand what role microbes play in a number of key diseases.

Mount Sinai Hospital, along with a Canada-wide consortium of researchers, was awarded $2.5 million over five years to further the research of Drs. Ken Croitoru and Mark Silverberg.

Dr. Croitoru, a clinician-scientist at Mount Sinai Hospital’s Zane Cohen Centre for Digestive Diseases, and a Professor of Medicine at the University of Toronto, Division of Gastroenterology, is the lead investigator of a prospective study of healthy people genetically at risk of developing Crohn’s disease. The study, funded by the CCFC and termed “The GEM Project,” is designed to identify a change in the gut bacteria or a change in the immune response in people who have IBD, before they develop disease. This may be the only way to identify the triggers that cause the disease, and will help lead to new strategies for improved diagnoses and treatments.

Since Dr. Croitoru and his team believe that the composition of bacteria in the gut is influenced by genes known to confer risk of IBD, the newly funded CIHR study will build on the CCFC GEM project by allowing the team to study an entire group of healthy individuals — many of whom carry gene variants that are known to be associated with development of Crohn’s disease.

“The idea is not just that bacteria live in our gut and cause disease, but that our bodies and our genes allow for certain types of bacteria — some good, some bad — to interact and influence development of diseases like Crohn's disease,” said Dr. Croitoru.

By assessing these individuals, Dr. Croitoru and his team can then study how specific human genes influence the makeup of the complex community of gut bacteria (or ‘microbiota’) in healthy people.

“Our ultimate goal is to identify a cause of inflammatory bowel disease like Crohn's and ulcerative colitis so a preventive therapy or even cure can be developed,” said Dr. Croitoru. “These studies are the first and necessary step to really changing the way we deal with patients who have inflammatory bowel disease, and will also affect people with many other complex diseases.”

Dr. Mark Silverberg is a gastroenterologist at Mount Sinai Hospital and a researcher affiliated with the hospital’s Zane Cohen Centre for Digestive Diseases and the Samuel Lunenfeld Research Institute. He holds the Gale and Graham Wright Research Chair in Digestive Diseases. Dr. Silverberg conducts leading-edge research to discover genetic markers and other biomarkers related to IBD, to allow more personalized approaches to its treatment.

In the past year, Dr. Silverberg has co-led major international projects designed to identify genetic markers associated with ulcerative colitis and childhood-onset IBD.  This research follows previous projects that have identified important genes related to adult-onset Crohn’s disease. Dr. Silverberg’s findings will provide critical information for advancing diagnoses and treatment plans for patients affected by IBD.

Dr. Silverberg recently received a three-year, $900,000 grant from the CCFC, to identify key genes underlying risk for the most aggressive forms of Crohn’s disease. He is leading a trial with investigators from the University of Calgary and others internationally, to ultimately help clinicians better predict Crohn's disease, identify high-risk patients, and develop a more personalized approach to treatment based on patients’ unique genetic signatures.

“Our work at Mount Sinai Hospital is focused on trying to understand whether a person’s genetic variants will have an impact on their disease: Is it going to be mild or severe, will it affect the kind of complications they might develop, will it affect how they respond to treatment,” said Dr. Silverberg. “We’re working on bringing genetic discoveries to patient management and improved patient care.”


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