Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
Solveig Runge, Silvia von Zedtwitz, Alexander M Maucher, Philipp Bruno, Lisa Osbelt, Bei Zhao, Anne Marleen Gernand, Till Robin Lesker, Katja Gräwe, Manuel Rogg, Christoph Schell, Melanie Boerries, Till Strowig, Geoffroy Andrieux, Benedikt Hild, Stephan P. Rosshart
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.