A Novel Zebrafish Model for Adherent-Invasive Escherichia Coli Indicates Protection from Infection by Treatment with Probiotic E. Coli Nissle

Adherent-invasive Escherichia coli (AIEC) is an opportunistic pathogen associated with major inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). AIEC is a human commensal but during unfavorable gastric conditions it exhibits pathogenic properties and induces inflammation in the gut, sometimes progressing to inflammation-induced colon cancer. The exact mechanisms for AIEC pathogenesis are still being discovered. As a human opportunistic pathogen, AIEC has few animal models. Recently, zebrafish have emerged as a useful model for studies of human pathogens. Here, a zebrafish model to study AIEC infection was developed. Bath inoculation with AIEC resulted in colonization and tissue disruption in the zebrafish gut. The gene expression of pro-inflammatory markers such as IL-1β, TNFα and IFNγ in intestinal cells of zebrafish was significantly induced by AIEC infection. An IBD marker, calprotectin, was significantly higher in the zebrafish gut during AIEC infection. The probiotic E. coli Nissle 1917 (EcN) was tested as a therapeutic and prophylactic against AIEC infection by co-inoculation, and reduced AIEC colonization, tissue damage and pro-inflammatory responses in zebrafish. Furthermore, EcN diminished the propionic acid-augmented hyper infection of AIEC in the zebrafish model. Thus, this study shows the efficacy of EcN against AIEC in a novel AIEC-zebrafish model.