Phage intervention improves colitis and response to corticosteroids by attenuating virulence of Crohn’s disease–associated bacteria

Authors:
Publisher website
Google Scholar
Abstract
Adherent-invasive Escherichia coli (AIEC) exhibits proinflammatory properties and has been implicated in the pathogenesis of Crohn’s disease (CD), a form of inflammatory bowel disease (IBD). Antibiotic use in CD lacks specificity and may worsen microbiome disruption, prompting interest in bacteriophages (phages) for targeted microbiome editing. Here, we identified HER259, a phage active against clinical AIEC isolates. HER259 ameliorated colitis in gnotobiotic models and attenuated the virulence of AIEC strain NRG857c, including suppression of the FimH adhesin through inversion of the fimS promoter to its “off” orientation. The effects were confirmed in CD-microbiota colitis models. Withdrawal of HER259 treatment led to reversion of the fimS promoter and reactivated colitis. The HER259 phage also enhanced the therapeutic effect of subtherapeutic budesonide independent of microbial drug metabolism. These findings support targeted phage therapy as an adjunct treatment approach in IBD, demonstrating modulation of bacterial virulence and improved response to conventional treatments that may reduce drug-related side effects.
Funding Information
  • Canadian Institutes of Health Research (183881)
  • Canadian Institutes of Health Research (RN279389)
  • Canadian Institutes of Health Research (35803)
  • Canadian Institutes of Health Research (203717)
  • Discovery Grants Program (ER22-17-067)

This publication has 54 references indexed in Scilit: