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Abstract

Microbial communities (a.k.a. the microbiota or microbiome) associated with mammals and other animals are essential to the biology of the host. The microbiome can modulate metabolism and immune functioning, and the disturbance of community structure and/or function can lead to dysbiosis, inflammation or disease. Extensive studies have been carried out in humans and lab mouse models with different emphases, while the study of mice in there natural environment (wild house mice) is yet under-represented, even though wild mice have a more similar ecology and biology to humans. In my thesis, the wild house mouse in Europe is used as a model for which numerous important factors influencing the gut microbiome are explored. First, we analyzed mice captured in eight different geographical regions of Western Europe and examined the relative importance of several components in shaping gut microbiome. We found geography to be the most significant factor influencing both the mucosal and luminal microbiome, with a comparatively weaker influence of host population structure and genetic distance, which was only significant in the mucosaassociated communities. Secondly, a separate analysis based on the luminal microbiome suggests the existence of "enterotypes" in wild mice, mirroring the findings in humans and chimpanzees. We experimentally tested newly captured wild mice and observed fast convergence to only one enterotype under a standardized diet. Additional functional metagenomic analysis and diet reconstruction based on stable isotope analysis both strongly support the determining role of diet in shaping enterotypes. In the third study, we focused on the effect of host hybridization on the gut microbiome between two subspecies of house mice (Mus musculus musculus and M. m. domesticus) from a transect of the hybrid zone in Bavaria, as well as artificial crosses between lab inbred strains. Hybrid mice have an intestinal microbiome distinct from their parental species in both setup, and with quantitative trait loci (QTL) mapping we identified transgressive phenotypes (bacterial abundances and comunity diversity) contributing to the distinct hybrid microbiome. Combined with additional immune and histopathological evidence, we propose that purifying selection acts to maintain a normal functioning microbiota, while in hybrids the distorted communities reflect genetic incompatibilities and may influence host fitness. Lastly, some primary efforts are devoted to studying candidate host-associated bacteria using a full genomic sequencing approach, where we begin to understand genomic variation of Staphylococcus epidermidis, a prominent skin-associated microbe, in the context of adaptation to the host.