Differential translocation of bacteriophages across the intestinal barrier in health and Crohn’s disease

Impaired intestinal barrier function is a major feature of Crohn's disease, leading to exacerbated inflammation in response to the microbiota. In this context, the translocation of intestinal bacteriophages (phages) and their effects on the host haven't been fully investigated. We use phage fluorescence imaging coupled with ex vivo, in vitro, and in vivo models that mimic physiological and inflammatory conditions and find that phages can translocate across the intestinal barrier without disrupting its integrity. While changes in the epithelial barrier integrity selectively impact phage translocation rates, alterations in the permeability of the vascular endothelium do not affect phage crossing. Virome analysis confirms that viral sequences shared between the blood and fecal samples of patients with Crohn's disease are more abundant than in healthy subjects, suggesting that a barrier defect facilitates intestinal phage translocation.