(Toronto, ON) Inflammatory bowel disease (IBD) is a painful condition that causes inflammation and ulcers in the intestine and colon. IBD affects over 200,000 Canadians (one in five), 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.
November: Crohn’s and Colitis Awareness Month
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 recently become a hot area of medical research.
Last spring, 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 including some at Mount Sinai Hospital. The goal is to understand what role microbes play in a number of key diseases.
Mount Sinai, 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, 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. To date, the GEM project has recruited over 1,700 healthy subjects at risk of developing Crohn’s disease and 11 have developed disease. The study has now expanded to include centres in the United States and Israel.
Since Dr. Croitoru and his team believe that the composition of gut bacteria 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. In the last year, over 800 subjects have been genotyped demonstrating that this group of individuals is genetically similar to patients with Crohn’s disease, helping to support the notion that this group will provide important insight into what triggers disease in individuals with a genetic susceptibility for Crohn’s.
“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.
Dr. Silverberg has been part of large, international efforts to identify all of the genes related to IBD. Building upon these successes, his lab is now focussed on finding a way to bring the genetic advances to helping patients living with IBD right now such as identifying markers that can predict disease prognosis.
Dr. Silverberg is leading a trial with investigators from the University of Calgary and UCLA to ultimately help clinicians better predict high-risk patients with Crohn’s disease so that they can be treated more actively to prevent complications. This will allow for a more personalized approach to treatment based on patients’ unique genetic signature. They are also looking for clues as to which patients develop rapid recurrence of Crohn’s disease after surgery to remove diseased bowel.
“Our work at Mount Sinai Hospital, one of the largest and best IBD programs in the world, is focused on trying to understand how 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.”
Ultimately, it is hoped that the critical work in IBD research being conducted by the gastroenterology and surgical group at Mount Sinai Hospital will improve the care of patients living with IBD now and eventually to finally understand the causes and preventions of these diseases.