A research team at McMaster University announced on July 8 the development of a targeted approach to treating inflammatory bowel disease using bacteriophages, viruses that infect specific bacteria, to disarm harmful microbes without disrupting the broader gut ecosystem.
The study, published in Science Translational Medicine and featured on the cover of the journal, involved collaboration between researchers from the Faculty of Engineering and the Faculty of Health Sciences. The team combined expertise in microbiome science and targeted antimicrobials to address challenges in gut health. Inflammatory bowel disease affects an estimated 300,000 Canadians, with rates continuing to rise, particularly among children. Canada has one of the highest rates of pediatric IBD in the world. Current treatments can be effective but may fail over time or require escalating doses that increase risk for serious side effects.
The research focused on adherent-invasive Escherichia coli (AIEC), a group of bacteria linked to inflammation in some people with Crohn's disease. Using E. coli strains isolated from patients with Crohn's disease, researchers used controlled experimental models to isolate how AIEC contribute to inflammation and explored ways to neutralize their harmful behavior without damaging beneficial bacteria.
"This kind of work depends on bringing multiple areas of expertise together," said Kyle Jackson, a Vanier Scholar and former graduate student who worked across both labs. "You need engineering, microbiology, immunology and clinical insight to understand how these systems interact with the gut's complex microbial ecosystem." To target AIEC specifically, the team turned to bacteriophages that infect bacteria with precision.
"Phages work like a lock-and-key system – each phage targets only certain bacteria. That precision gives us a way to intervene without wiping out the entire microbiome," said Zeinab Hosseinidoust, associate professor in the Department of Chemical Engineering and School of Biomedical Engineering. The identified phages did not eliminate AIEC entirely but altered their behavior by suppressing a molecular mechanism that helps them attach to gut lining and trigger immune responses.
"The bacteria were still there but they lost the traits that drive inflammation. We like to think of it as knocking out a few teeth. The bacteria can't do as much damage anymore," said Hosseinidoust.
The study also found that combining phage therapy with lower-than-standard doses of steroid treatment produced benefits comparable to higher doses alone—a positive collaboration between phage therapy and non-antibiotic drugs reported for the first time by this group. The findings suggest potential for precision medicine approaches; bacterial functions targeted by phages can be measured in stool samples and may help identify patients who could benefit most from this therapy.
"If we can identify which patients carry the harmful bacterial function, we could, in future, intervene with a targeted therapy designed specifically to turn down that activity," said Verdu. "This is what personalized medicine should look like: matching the right biological tool to the right patient," said Hosseinidoust.
Next steps include evaluating broader collections of bacterial strains from IBD patients and developing combinations of phages as part of efforts toward human trials.
