Isolation by distance promotes gut microbial strain divergence in wild mouse populations.

Bacterial species within the mammalian gut microbiota exhibit considerable strain diversity associated with both geography and host genetic ancestry. However, because geography and ancestry are typically confounded, disentangling their contributions to the divergence of gut bacterial strains has remained challenging. Here we show that isolation by distance (IBD) promotes gut bacterial strain divergence within host species independently of host ancestry. Joint profiling of gut bacterial and mitochondrial genomes from wild-living populations of deer mice (Peromyscus maniculatus) sampled across the USA revealed significant IBD in 27 predominant gut bacterial species, including Muribaculaceae and Lachnospiraceae spp., but limited evidence for co-inheritance of gut bacterial genomes with mitochondria during the diversification of mouse populations. Spore-forming gut bacterial species exhibited reduced IBD, suggesting that adaptations facilitating bacterial dispersal can lessen geographic structuring of strain diversity. In contrast to conspecific hosts sampled at the same field site, hosts of different rodent genera sampled in sympatry with deer mice harboured divergent strains within shared gut bacterial species. These results indicate that geographic distance mediates the early stages of gut bacterial strain divergence between conspecific hosts, whereas effects of host ancestry on strain-level microbiota composition emerge over longer evolutionary timescales, such as those separating host genera.