A bacteriophage-conditional mouse model reveals the impact of phages within a conventionally colonized gut microbiota

The significance of bacteriophages in the gut microbiota remains poorly understood due, in part, to an absence of an animal model that allows for comparative study of conditions with or without phages while retaining the microbial diversity attained by conventional colonization. We describe a mouse model that uses a broadly available chemical compound, acriflavine, to preferentially deplete virulent phages from the gut without significantly impacting gut bacteria. We then show that gut phage density can be reconstituted by oral gavage. Using this bacteriophage-conditional (BaCon) mouse model, we reveal that while phages have comparatively minimal impact during equilibrium conditions, they increase the potency of ampicillin against commensal gut bacteria. Collectively, our work presents an animal model that can be leveraged to conditionally study the role of phages in complex, physiologically relevant systems and further identifies virulent gut phages as potential sources of bacterial variability during major perturbations.