In the chronic inflammatory bowel disease known as Crohn's, many therapies aim to curb inflammation in the gut. But common antibiotics also hit beneficial microbes and further weaken a microbiome that is already out of balance. A team at McMaster University in Hamilton, Canada, is now taking a far more targeted route — and leaves the gut's bacterial community largely intact.
At the centre is a group of Escherichia coli bacteria described as adherent-invasive (AIEC). They cling to the intestinal wall, invade its cells and thereby fuel the inflammation that, for many patients, comes with diarrhoea and cramping pain. Rather than killing these microbes, the researchers disarmed them with a bacteriophage — a virus that infects only very specific bacteria.
A lock-and-key principle
The phage they used, named HER259, flips a genetic switch called fimS in the bacteria. As a result, the microbes lose their ability to latch onto and invade intestinal cells; they remain present but do little harm. When the team withdrew the phage, the switch flipped back and the inflammation returned in the animal model. In mice with gut inflammation the disease subsided under treatment; at the same time the animals responded better to a low-dose steroid therapy, which could reduce the side effects of such drugs.
The work, published in the journal Science Translational Medicine and featured on its cover, grew out of a collaboration between microbiome specialists led by Elena Verdu and the phage-focused group of Zeinab Hosseinidoust.
For now this is a study in mice; clinical trials are needed before any use in humans. Yet the approach is promising on several counts: inflammatory bowel diseases are rising worldwide — in Canada alone around 300,000 people are affected, with especially high rates among children. And because the decisive bacterial trait can be measured in stool samples, it may one day be possible to identify which patients would benefit most from such a phage therapy.