Pervasive bacterial and prophage hybridization during chronic gut inflammation

Summary Inflammatory bowel diseases (IBD) are modulated by microbiota composition, host genetics, and environmental factors 1 . Humans and other mammals are colonized by multiple strains of Escherichia coli , a species that expands in abundance in IBD patients 2 . The state of chronic inflammation characteristic of IBD is expected to intensify selective pressures on the gut microbial community, leading to distinct adaptive trajectories among its constituents. Here we couple in vivo experimental evolution with short- and long-read sequencing to test this hypothesis at the level of mutation and horizontal gene transfer (HGT). By colonizing IL10KO mice, a model of IBD 3 , and healthy wild-type mice with two strains of E. coli , we show that the tempo and mode of evolution are strain-specific and strongly shaped by host inflammatory status. Unique mutations associate with host inflammatory status independently of microbiota composition, and rates of transfer are diagnostic of chronic inflammation. Extensive transduction events occur in the inflamed gut, giving rise to hybrid clones that form a new genetic lineage, one that becomes dominant in this disease context. The high levels of recombination between prophages uncovered here point to a critical role of HGT and viral evolution in IBD.