Inflammatory bowel disease (IBD) affects millions around the world, and scientists seem to be in a never-ending race to find targeted and more efficient treatments. Now, researchers say they’ve developed the first phage combination therapy to target and clamp down on harmful gut bacteria associated with the condition.
Antibiotics are frequently prescribed to patients with this disease, but these forms of treatment aren’t always equipped to tackle specific bacteria that’s causing harm. The issue with antibiotics no matter what the ailment is that they kill healthy bacteria that supports immunity and gut integrity in addition pathogenic bacteria. The team of researchers leading this work would like to explore a more functional alternative.
“This proof-of-concept study utilizes phages as a precision weapon in suppressing a group of commensal strains contributing to IBD,” says corresponding author Eran Elinav, of the Weizmann Institute of Science and the Microbiome & Cancer Division, German National Cancer Center.
The team of researchers from around the world compared gut environments of 537 IBD patients to healthy gut controls of people enrolled in studies across France, Israel, the United States, and Germany. They discovered that generally speaking, IBD patients had strains of the bacterium Klebsiella pneumoniae (Kp) residing in their gut. By then transplanting the bacterium into mice, the scientists discovered that mice developed extreme inflammation and tissue damage. This finding suggests that Kp plays an active role in the severity of inflammatory bowel disease.
Next steps involved scanning and isolating thousands of bacteriophages, viruses that target and damage bacteria, from environmental samples. Researchers successfully pinpointed around 40 phages that seem to be effective against the problematic Kp strains, even the ones that have already developed phage resistance. They then tested the phages through mixing and matching to determine the best combination for treatment. Ideally, the best combination is one that can target bacteria resistant to phages to stop them from continuously gaining ground and spreading around.
Ultimately, the researchers identified a combination consisting of five different phages. This successfully shut down Kp strain activity in test tubes and mice with IBD modification.
Study authors hope to further build on these findings, even to help treatment efforts with other diseases. “Our vision is that this new modality could potentially be developed and applied against a number of other IBD-associated bugs, and also against commensals that are involved with other diseases, including obesity, diabetes, cancer, neurodegenerative diseases, and more,” explains Elinav.
Phase 1 clinical trials are now underway by the group, who are testing their discovery in 18 healthy people. It showed promising results, suggesting that the phage compound can withstand stress that could be posed on the gut when taking antacids, and had no negative effect on healthy microbes. They are now planning for phase II work.
This study is published in the journal Cell.