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

Abstract

Impaired intestinal barrier function is a major feature of Crohn's disease (CD), leading to exacerbated inflammation in response to the microbiota. In this context, the translocation of intestinal bacteriophages (phages) and their effects on the host have been little investigated. We used phage fluorescence imaging coupled with ex-vivo and in-vitro models that mimic physiological and inflammatory conditions and found that phages can translocate across the intestinal barrier without disrupting its integrity. Although the translocation rate across the intestinal epithelium depended on phage morphology and the condition of the barrier, these factors did not influence the crossing of phage across the vascular endothelium. Virome analysis confirmed that viral sequences shared between blood and stool samples are more abundant in CD patients than healthy subjects, indicating that a barrier defect facilitates phage translocation from the gut to the bloodstream.