Identification and Characterization of the Wild Mouse Gut Microbiome as the Optimal Standard for Laboratory Mice

This technology includes identification of the wild mouse microbiome as a method to increase resistance to lethal viral infection. We establish that the gut microbiome of barrier-raised C57BL/6 mice is dysbiotic compared to that of their outbred, wild-living progenitors, Mus musculus domesticus. We find that the multigenerational offspring of pregnant germfree C57BL/6 mice reconstituted with the gut microbiome of wild mice exhibit a less inflammatory response and increased survival following influenza A virus infection. Thus, replacing the gut microbiome of laboratory mice with the wild mouse microbiome via fecal material transfer increases resistance to lethal viral infection. By simply restoring the natural microbial identity of laboratory mice, we crease a more physiologically balanced and biologically relevant model. We propose that the natural “gold-standard” wild mouse microbiome become the standard used in laboratory mice, with obvious applications to other animal models.