Studies of the victims of the Walkerton, Ont. tainted drinking water tragedy have led researchers to discover DNA variations in genes that increase the risk of developing post-infectious irritable bowel syndrome (PI-IBS). The sheer scale of infection and the recording of the health of Walkerton’s citizens gave a team of researchers a unique opportunity to study the origin of this disorder.
“Although the exact cause of PI-IBS remains unknown, we now know for the first time that, in addition to the environmental trigger, genetic factors are also playing a critical role in the development of this disease,” explains McGill PhD Alexandra-Chloé Villani, who led the team under the direction of principal investigators John K. Marshall (McMaster) and Denis Franchimont (formerly of McGill). Stephen Collins (McMaster) also collaborated.
Almost 10 years ago, the municipal water supply of Walkerton was contaminated with E. coli and Campylobacter jejuni, leading to a public health disaster. Seven people died and 2,300 suffered symptoms, including bloody diarrhea. Of these 2,300, 36 per cent developed PI-IBS, giving the town the highest incidence of PI-IBS ever reported.
PI-IBS is a functional bowel disorder that has an acute onset after an episode of gastroenteritis. “These patients suffer from chronic abdominal pain, discomfort, bloating and disturbed defecation in the absence of any detectable structural or biochemical abnormalities,” said Marshall, a gastroenterologist. “After the exclusion of known organic disorders, like Crohn’s disease and ulcerative colitis, such patients are diagnosed with PI-IBS.”
“The biological implications of the identified genetic risk factors emphasize the important roles of the gut microbial flora, intestinal barrier function and inflammatory pathways in contributing to the onset of PI-IBS,” Villani explained. Though these results will not lead to any new short-term treatments for PI-IBS, Marshall is confident that in the longer term the research will lead to better patient care, including potentially novel therapeutic targets for research, as well as improved medical decision-making (“risk stratification”) concerning victims of future outbreaks.
The details of the study will be published in the March edition journal Gastroenterology (available online at gastrojournal.org). The study was supported by the Crohn’s & Colitis Foundation of Canada (CCFC) and the Ontario Ministry of Health and Long-Term Care. McGill’s Villani is affiliated with the McGill University and Genome Quebec Innovation Centre. Marshall and Collins are both at the Michael G. DeGroote School of Medicine, McMaster University. Marshall is Associate Professor of Medicine, a Full Member of the Farncombe Family Digestive Health Research Institute and Head of Clinical Research for the Division of Gastroenterology. He is also an active consultant gastroenterologist at Hamilton Health Sciences. Collins is a Professor of Medicine and Associate Dean for Research, Faculty of Health Sciences and holds the GlaxoSmithKline Chair in Gastroenterology. Franchimont, now with the Erasme Hospital in Brussels, Belgium, was a Canada Research Chair formerly affiliated with the Gastroenterology Department at McGill University Health Centre (MUHC).
About the McGill University and Génome Québec Innovation Centre:
The McGill University and Génome Québec Innovation Centre is financed by Genome Canada and the Ministère du Développement économique, de l’innovation et de l’exportation of Quebec, and provides complete DNA analysis services, from a few samples to several tens of thousands per week. Ambitious DNA sequencing projects carried out over the past five years are testimony to Génome Québec’s ability to provide data of exceptional quality in the pursuit of various genomics studies. Large-scale genomics projects at the Innovation Centre are highly integrated together on three platforms: sequencing, genotyping and functional genomics supported by an infrastructure and unique expertise in bioinformatics. High-quality protein separation and analysis services are also provided by the proteomics platform.
About McMaster University and the Farncombe Family Digestive Health Research Institute:
The Farncombe Family Digestive Health Research Institute is an integrated group of clinical and basic scientists dedicated to understanding the causes of chronic digestive diseases. The Institute is focused on developing new strategies for the diagnosis, treatment and prevention of intestinal diseases such as Crohn’s disease and ulcerative colitis, which will have global benefits. Formerly known as the Intestinal Diseases Research Program (IDRP), the newly established Institute was established with a $15-million gift from the Farncombe family. The generous contribution, which includes four endowed chairs and infrastructure capital, will ensure the long-term success of the Institute and enhance its role as an innovative training environment. For more than 20 years, McMaster’s Intestinal Diseases Research Program has garnered an international reputation as one of the top 10 gastrointestinal research groups in the world. The growth in research funding, faculty awards and now the expansion into a Research Institute is a testament to the critical role McMaster researchers are playing in the study of gastrointestinal diseases.