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The gut microbial communities of mammals have codiversified with host species, and changes in the gut microbiota can have profound effects on host fitness. Therefore, the gut microbiota may drive adaptation in mammalian species, but this possibility is underexplored. Here, we show that the gut microbiota has codiversified with mice in the genus Mus over the past ∼6 million years, and we present experimental evidence that the gut microbiota has driven adaptive evolution of the house mouse, Mus musculus  domesticus Phylogenetic analyses of metagenome-assembled bacterial genomic sequences revealed that gut bacterial lineages have been retained within and diversified alongside Mus species over evolutionary time. Transplantation of gut microbiotas from various Mus species into germfree M. m. domesticus showed that foreign gut microbiotas slowed growth rate and upregulated macrophage inflammatory protein in hosts. These results suggest adaptation by M. m. domesticus to its gut microbiota since it diverged from other Mus species. IMPORTANCE The communities of bacteria that reside within mammalian guts are deeply integrated with their hosts, but the impact of this gut microbiota on mammalian evolution remains poorly understood. Experimental transplantation of the gut microbiota between mouse species revealed that foreign gut microbiotas lowered the host growth rate and upregulated the expression of an immunomodulating cytokine. In addition, foreign gut microbiotas increased host liver sizes and attenuated sex-specific differences in host muscle and fat content. These results suggest that the house mouse has adapted to its species-specific gut microbiota.

Experimental Evidence for Adaptation to Species-Specific Gut Microbiota in House Mice