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Schlagwörter:
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Zusammenfassung:
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.
