IDENTIFYING NOVEL NICHES OF ADHERENT-INVASIVE ESCHERICHIA COLI EXPANSION DURING ANTIBIOTIC TREATMENT

Abstract

Antibiotic use is a major Crohn’s disease (CD) risk factor. By perturbing the microbiome, antibiotics can promote the expansion of disease-aggravating microbes, including adherent-invasive Escherichia coli (AIEC). However, little is known about whether certain geographical regions of the gut are more susceptible to antibiotic-induced AIEC expansion. Here, we report that the antibiotic vancomycin enables AIEC colonization of ileal Peyer’s patches, leading to increased inflammation. Using a mouse model, we found that vancomycin treatment in naïve mice creates a niche for Escherichia in ileal Peyer’s patches. AIEC appear to exploit this niche, as vancomycin promoted a tropism of AIEC for Peyer’s patches. Alongside this expansion, we observed that the ileum of AIEC-expanded mice exhibited significantly worsened pathology relative to controls. Furthermore, AIEC-expanded mice displayed higher levels of pathology around Peyer’s patches, suggesting that AIEC colonization of Peyer’s patches precipitates focal inflammation of this lymphoid compartment. Deletion of flagellin and antimicrobial peptide resistance genes attenuated AIEC burden and pathology in Peyer’s patches, suggesting that these virulence factors are involved in colonization and focal inflammation in this niche. Overall, our findings reveal previously unknown niches and consequences of AIEC expansion that may inform the use of antibiotics in subsets of CD patients and improve CD management strategies.