Host-Specific Adaptive Diversification of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli

Crohn’s disease (CD) is an inflammatory bowel disease influenced by bacteria. Adherent-invasive E. coli (AIEC) is associated with CD, yet the adaptations facilitating AIEC gut colonization are unknown. AIEC isolates exhibit high genetic diversity, suggesting strains evolve independently across different gut environments. We tracked the adaptive evolution of AIEC in a murine model of chronic colonization across multiple hosts and transmission events. We detected evolved lineages that outcompeted the ancestral strain in the host through independent mechanisms. One lineage was hypermotile because of a mobile insertion sequence upstream of the master flagellar regulator, flhDC, which enhanced AIEC invasion and establishment of a mucosal niche. Another lineage outcompeted the ancestral strain through improved use of acetate, a short-chain fatty acid in the gut. The presence of hypermotile and acetate-consuming lineages discriminated E. coli isolated from CD patients from healthy controls, suggesting an evolutionary trajectory that distinguishes AIEC from commensal E. coli. [Display omitted] •Host-to-host transmission selects for AIEC with greater motility and acetate metabolism•Hypermotility mediates higher invasive and inflammatory host responses•Improved acetate utilization is a common trait for many hypomotile isolates•Crohn’s disease E. coli isolates also exhibit increased motility and acetate utilization Crohn’s disease is associated with adherent-invasive E. coli (AIEC), but the factors promoting AIEC colonization are unclear. Elhenawy et al. show that murine host-to-host transmission selects for adaptive diversification of AIEC, with enhanced bacterial motility and acetate metabolism. E. coli isolates from Crohn’s disease patients similarly exhibit these adaptive features.