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The gut microbiome shapes host health through a complex network driven by both host‒microbe and microbe‒microbe interactions. Disruption of these interactions, often referred to as dysbiosis, is as...

Phages are key members of the gut microbiome, but the understanding of their biological significance for host health lags behind their bacterial hosts. In this study, we demonstrate the use of a phage-infection model using defined, synthetic microbial communities that colonize the intestinal tract of mice. We uncovered that spontaneous inversions in the genome of Bacteroides uniformis perpetually generate subpopulations, which are either sensitive or resistant to phage infection, allowing for the coexistence of predator and prey in this species. Phage infection demonstrated broad impacts on community structure and metabolism in animals, which are not easily predicted by the exclusion of the viral host. This research demonstrates a tractable approach through which the impacts of phage on both the microbiome and mammalian host can be deciphered.