McMaster University investigators have opened up a new area of research in the study of Crohn’s Disease, a chronic inflammatory bowel disease that afflicts over 100,000 Canadians, one of the highest rates worldwide.
Led by Brian Coombes, Associate Professor in the Department of Biochemistry and Biomedical Sciences and member of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR), his group has been studying a variant of E. coli called adherent-invasive E. coli (AIEC) that is associated with human Crohn’s Disease. In their new work, Coombes’ group developed a new mouse model that showed that Crohn’s-associated E. coli could cause chronic infection in the mouse gut. Interestingly, after infection the mice developed chronic gut inflammation that resembled that seen in human Crohn’s Disease. This new model will allow researchers to understand the effects of chronic colonization on the host immune system and how this might play a role in disease development.
“Up to now, animal models of Crohn’s Disease often rely on the use of genetically-modified mice that are hard to obtain, or use chemicals that cause inflammation in the gut. Previous work infecting genetically modified mice with this E. coli in the presence of pro-inflammatory chemicals lead to an infection that was fatal over a one-week period,” says Coombes “Obviously, this is not a desirable model if you are trying to understand a chronic human disease.”
Coombes’ goal was to develop a new animal model that would allow researchers to study the effects of chronic infection: “In other words,” he says, “could we take our strain of Crohn’s-associated E. coli and colonize mice for life so we could study the long-term consequences on an animal carrying this particular E. coli in their intestine. We achieved that and successfully developed a chronic colonization infection model in five conventional mouse lines, allowing us to understand the host response in greater detail.”
Crohn’s Disease belongs to a group of diseases called Inflammatory Bowel Disease (IBD), affecting one in every 160 Canadians. Even more common is Irritable Bowel Syndrome (IBS), which in some cases can put people at greater risk for IBD. An estimated five million Canadians suffer from IBS, or about one in seven people. “We’re very interested in trying to understand if there is a microbial link to IBS as well.”
Little is known about the definitive causes of Crohn’s Disease. While links have been made to genetic predispositions, there are many who suffer from Crohn’s who have no known hereditary link to the disease.
“There is an accepted microbiological link to Crohn’s disease and there is good data from human clinical studies and also animal studies suggesting that the presence of bacteria is necessary for the expression of Crohn’s disease symptoms,” Coombes says.
“This work opens up a whole new area of research where we can start to understand the host response to a bacteria linked to Crohn’s Disease,” he says. “And because we have the genome sequence of the bacteria we can begin to ask questions like what are the genes present in this particular bacteria that make it invasive, how does it colonize for long periods of time, and why is it so pro-inflammatory?”
His ultimate goal is to apply these findings to the human condition, to see whether these bacteria might be the cause of the chronic inflammation seen in humans with Crohn’s disease. “There’s clearly lots of work to do, but we’re excited about the direction it’s heading in.”
The paper is published in Nature Communications.