Mcmaster researchers develop targeted phage therapy for inflammatory bowel disease

A research team at McMaster University has developed a targeted approach to treating inflammatory bowel disease (IBD) 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, brings together researchers from the Faculty of Engineering and the Faculty of Health Sciences, combining expertise in microbiome science and targeted antimicrobials to tackle a complex challenge in gut health. 

IBD 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. Although current treatments can be effective, they can fail long-term or require escalating doses, increasing the risk of serious side effects. 

IBD is shaped by a combination of genetics, immune responses and the gut microbiome. The research team focused on a group of bacteria known as adherent-invasive Escherichia coli (AIEC), which have been linked to inflammation in some people with Crohn's disease. These bacteria can be difficult to identify and selectively target, making them an important test case for more precise microbiome-based therapies. 

One challenge is that AIEC are defined by what they do, not simply by how they appear in a microbiome analysis. To identify them, we need to test their behaviour, such as their ability to adhere to and invade intestinal cells and persist in immune cells."

Elena Verdu, professor in the Department of Medicine and director of the Farncombe Family Digestive Health Research Institute

Working with E. coli strains isolated from patients with Crohn's disease, the team used controlled experimental models to isolate how AIEC contribute to inflammation and explore ways to neutralize their harmful behaviour without damaging beneficial bacteria. 

The project reflects a uniquely collaborative research environment at McMaster. The Verdu lab focuses on the role of the gut microbiome in human health and disease, while the Hosseinidoust lab specializes in targeted antimicrobials, particularly bacteriophages. By working closely across disciplines and leveraging McMaster's axenic research facilities, which allow scientists to study the microbiome under highly controlled conditions, the teams were able to connect bacterial behaviour, immune responses and therapeutic design in ways that would be difficult to achieve in isolation.

"This kind of work depends on bringing multiple areas of expertise together," says 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 without collateral damage, the team turned to bacteriophages, or phages, which are naturally occurring viruses that infect bacteria with remarkable 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," explains Zeinab Hosseinidoust, associate professor in the Department of Chemical Engineering and the School of Biomedical Engineering. 

The team identified and characterized phages that selectively target AIEC strains isolated from patients with IBD and found that this approach significantly reduced gut inflammation. 

The phages did not eliminate the bacteria entirely. Instead, they altered their behaviour by supressing a molecular "grappling hook" that helps AIEC attach to the gut lining and trigger immune responses. When that virulence mechanism was turned off, inflammation subsided. 

"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," says Hosseinidoust. 

The researchers also found that phage therapy enhanced the effectiveness of a commonly used steroid treatment for IBD. When combined with the phage, a lower-than-standard dose produced benefits comparable to higher doses of the drug alone. While phages have previously been shown to increase the effectiveness of antibiotics, this is the first time a positive collaboration between phage and a non-antibiotic drug has been reported. 

The findings point to a precision‑medicine approach for IBD. The bacterial function targeted by the phage can be measured in stool samples and was found to be higher in a subset of patients with Crohn's disease, suggesting a potential way to identify those who could benefit most from this therapy.

"If we can identify which patients carry the harmful bacterial function, we could, in the future, intervene with a targeted therapy designed specifically to turn down that activity," says Verdu. 

"This is what personalized medicine should look like: matching the right biological tool to the right patient," says Hosseinidoust.

Next steps for the team include evaluating broader collections of bacterial strains from IBD patients and developing combinations of phages - work that brings the approach closer to human trials.