Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype

Solveig Runge (), Silvia Zedtwitz, Alexander M. Maucher, Philipp Bruno, Lisa Osbelt, Bei Zhao, Anne M. Gernand, Till R. Lesker, Katja Gräwe, Manuel Rogg, Christoph Schell, Melanie Boerries, Till Strowig (), Geoffroy Andrieux (), Benedikt Hild () and Stephan P. Rosshart ()
Additional contact information
Solveig Runge: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Silvia Zedtwitz: Faculty of Medicine
Alexander M. Maucher: Faculty of Medicine
Philipp Bruno: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Lisa Osbelt: Helmholtz Center for Infection Research
Bei Zhao: Faculty of Medicine
Anne M. Gernand: Faculty of Medicine
Till R. Lesker: Helmholtz Center for Infection Research
Katja Gräwe: Medical Center - University of Freiburg, Faculty of Medicine
Manuel Rogg: Medical Center - University of Freiburg, Faculty of Medicine
Christoph Schell: Medical Center - University of Freiburg, Faculty of Medicine
Melanie Boerries: University of Freiburg
Till Strowig: Helmholtz Center for Infection Research
Geoffroy Andrieux: University of Freiburg
Benedikt Hild: Medical Faculty, University of Duisburg-Essen
Stephan P. Rosshart: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Conventional laboratory mice housed under specific pathogen-free (SPF) conditions are the standard model in biomedical research. However, in recent years, many rodent-based studies have been deemed irreproducible, raising questions about the suitability of mice as model organisms. Emerging evidence indicates that variability in SPF microbiota plays a significant role in data inconsistencies across laboratories. Although efforts have been made to standardize microbiota, existing microbial consortia lack the complexity and resilience necessary to replicate interactions in free-living mammals. We present a robust, feasible and standardizable approach for transplanting natural gut microbiota from wildlings into laboratory mice. Following engraftment, these TXwildlings adopt a structural and functional wildling-like microbiota and host physiology toward a more mature immune system, with characteristics similar to those of adult humans. We anticipate that adopting wild mouse-derived microbiota as standard for laboratory mouse models will improve the reproducibility and generalizability of basic and preclinical biomedical research.

Date: 2025
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DOI: 10.1038/s41467-025-60554-2

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