Targeted phages suggest novel precision treatment for inflammatory bowel disease

A McMaster University team has shown that bacteriophages can disarm inflammation-linked gut bacteria without destroying the wider microbiome, in research that could support more precise treatment for Crohn’s disease

Researchers at McMaster University, Hamilton, Ontario, Canada, have developed a targeted bacteriophage approach to treat inflammatory bowel disease (IBD) by disarming harmful gut bacteria without disrupting the broader gut microbiome.

The study brought together researchers from the university’s Faculty of Engineering and Faculty of Health Sciences. The work combined microbiome science, immunology and targeted antimicrobial design to address a long-standing challenge in gut health which was how to control any disease-associated bacteria without damaging the wider beneficial microbes in the gut biome.

IBD affects an estimated 300,000 Canadians, with rates continuing to rise, particularly among children. Canada has one of the world’s highest rates of paediatric IBD. Although current treatments can prove effective, many patients lose response over time or require higher doses, increasing the risk of serious side effects.

The researchers focused on adherent-invasive Escherichia coli (AIEC), a group of bacteria linked to inflammation in some people with Crohn’s disease. These bacteria are difficult to identify because their importance depends on their behaviour rather than their genetic profile alone.

“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,” said Dr. Elena Verdu, professor in the department of medicine and director of the Farncombe Family Digestive Health Research Institute.

Using Escherichia coli strains isolated from patients with Crohn’s disease, the team investigated how AIEC contribute to inflammation and explored ways to neutralise harmful bacterial behaviour without affecting beneficial bacteria.

The project combined Verdu’s expertise in the gut microbiome with the laboratory of Dr. Zeinab Hosseinidoust which specialises in targeted antimicrobials and in particular bacteriophages. McMaster’s axenic research facilities* enabled the researchers to study bacterial behaviour, immune responses and potential therapies under tightly controlled conditions.

“This kind of work depends on bringing multiple areas of expertise together. You need engineering, microbiology, immunology and clinical insight to understand how these systems interact with the gut’s complex microbial ecosystem,” Dr. Kyle Jackson, a Vanier Scholar and former graduate student who worked across both laboratories, said.

The researchers identified bacteriophages that selectively targeted AIEC strains from patients with IBD. Rather than eliminating the bacteria, the phages suppressed a molecular mechanism that enables AIEC to attach to the gut lining and trigger immune responses. This reduced gut inflammation in experimental models.

“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,” Hosseinidoust said.

The team also found that phage therapy enhanced the effect of a commonly used steroid treatment for IBD. A lower-than-standard steroid dose combined with the phage produced benefits comparable to higher steroid doses alone. The researchers said this was the first report of a positive interaction between a phage and a non-antibiotic drug.

The findings suggest a precision medicine approach for IBD whereby the bacterial function targeted by the phage can be detected in stool samples and was more common in a subset of patients with Crohn’s disease, raising the prospect of identifying patients most likely to benefit. The team’s next steps include evaluation of larger collections of bacterial strains and development of phage combinations to move the approach closer to human trials.

* An axenic research facility is a laboratory or controlled research environment designed to maintain axenic cultures, meaning organisms that are grown in the complete absence of any other living organisms.

For further reading please visit: 10.1126/scitranslmed.adz4589