Closely related host species share similar symbionts, but the effects of host genetic admixture and environmental conditions on these communities remain largely unknown. We investigated the influence of host genetic admixture and environmental factors on the intestinal prokaryotic and eukaryotic communities (fungi, parasites) of two house mouse subspecies (Mus musculus domesticus and M. m. musculus) and their hybrids in two settings: (i) wild-caught mice from the European hybrid zone and (ii) wild-derived inbred mice in a controlled laboratory environment before and during a community perturbation (infection). In wild-caught mice, environmental factors strongly predicted the overall microbiome composition. Subspecies' genetic distance significantly influenced the overall microbiome composition, and each component (bacteria, parasites and fungi). While hybridization had a weak effect, it significantly impacted fungal composition. We observed similar patterns in wild-derived mice, where genetic distances and hybridization influenced microbiome composition, with fungi being more stable to infection-induced perturbations than other microbiome components. Subspecies' genetic distance has a stronger and consistent effect across microbiome components than differences in expected heterozygosity among hybrids, suggesting that host divergence and host filtering play a key role in microbiome divergence, influenced by environmental factors. Our findings offer new insights into the eco-evolutionary processes shaping host-microbiome interactions.

Department of Ecological Dynamics Leibniz Institute for Zoo and Wildlife Research Alfred Kowalke Straße 17 Berlin 10315 Germany

Department of Interdisciplinary Life Sciences Research Institute of Wildlife Ecology University of Veterinary Medicine Vienna Savoyenstraße 1 Vienna A 1160 Austria

Department of Molecular Parasitology Institute for Biology Humboldt University Berlin Philippstr 13 Haus 14 Berlin 10115 Germany

Division of Computational Systems Biology Center for Microbiology and Ecological Systems Science University of Vienna Djerassipl 1 Vienna 1030 Austria

Experimental and Clinical Research Center a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité Universitätsmedizin Berlin Berlin Germany

Experimental and Clinical Research Center Charité Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Lindenberger Weg 80 Berlin 13125 Germany

Institute of Ecology Chair of Planning related Animal Ecology Technische Universität Berlin Rothenburgstr 12 Berlin 12165 Germany

Max Delbrück Center for Molecular Medicine in the Helmholtz Association Robert Rössle Str 10 Berlin 13125 Germany

Research Facility Studenec Institute of Vertebrate Biology Czech Academy of Sciences Brno Czech Republic

Research Group Ecology and Evolution of Molecular Parasite Host Interactions Leibniz Institute for Zoo and Wildlife Research Alfred Kowalke Straße 17 Berlin 10315 Germany

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Eco-evolutionary dynamics of host-microbiome interactions in a natural population of closely related mouse subspecies and their hybrids