The factors influencing the interaction between phages and bacteria, as well as their long-term coexistence, remain poorly investigated within the human microbiome. In this study, we presented a phage-resistance mechanism, which is achieved through an episymbiont-mediated modulation of gene expression in host bacteria, thus affecting their susceptibility to phage predation. More significantly, our study demonstrated that through modulating its host bacteria susceptibility to phage predation, oral episymbiont Saccharibacteria promotes the long-term coexistence of its host bacteria and phage within the human oral microbiome by creating a “source-sink” dynamic between these two antagonistic microbial entities.
