The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages

The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistence. Coexistence was not dependent on the development of phage-resistant clones nor on the ability of phages to extend their host range. Instead, our data suggest that phage-inaccessible sites in the mucosa serve as a spatial refuge for bacteria. From there, bacteria disseminate in the gut lumen where they are predated by luminal phages fostering the presence of intestinal phage populations. The heterogeneous biogeography of microbes contributes to the long-term coexistence of phages with phage-susceptible bacteria. This observation could explain the persistence of intestinal phages in humans as well as the low efficiency of oral phage therapy against enteric pathogens in animal models and clinical trials. [Display omitted] •Bacteriophage/bacteria coexistence is reproduced in murine gut with synthetic microbiota•Bacteriophage resistant clones are not detected over time throughout the gut•Coexistence is not linked to off-target bacteriophage amplification•Spatial distribution and source-sink dynamics support phage-bacteria coexistence In the gut microbiota of mammals, the long-term coexistence of antagonistic populations of bacteriophages and bacteria remains unresolved. Lourenço et al. show that the uneven spatial distribution of bacteriophages in the gut creates bacterial refuges, which may hinder the overall efficacy of phage therapy targeting intestinal pathogens.