Current and emerging therapeutic strategies targeting adherent-invasive Escherichia coli in Crohn’s disease: a review

Abstract

Considerable evidence has accumulated over the past two decades demonstrating that Escherichia coli, specifically adherent-invasive E. coli, contributes to the pathogenesis of Crohn's disease. Adherent-invasive E. coli can adhere to and invade intestinal epithelial cells, survive, and replicate within macrophages, thereby enabling a key mechanism that induces chronic inflammation. Despite extensive knowledge of the molecular interactions between adherent-invasive E. coli and the host from these studies, translating this knowledge into targeted therapy remains limited.In this review, we summarize current and proposed treatments to prevent or eliminate adherent-invasive E. coli colonization. We provide a theoretical framework that categorizes these strategies into four main pillars: direct pathogen targeting (e.g., antibiotics, phage therapy), blockade of bacterial virulence factors (e.g., anti-adhesive compounds, QseC inhibitors), host-mediated clearance (e.g., autophagy inducers), and ecological intervention/restoration (e.g., fecal microbiota transplantation, Probiotic, Prebiotic and Probiotics). Finally, we discuss new modalities, including predatory bacteria, siderophore immunization, and other approaches. This review identifies the latest weapons against adherent-invasive E. coli, synthesizes experimental and clinical evidence to provide a comprehensive view of this evolving therapeutic arsenal, and offers ideas for future treatment of Crohn's disease.