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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Solveig Runge, Silvia von 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, Stephan P. Rosshart
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60554-2
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850221771408539648
author Solveig Runge
Silvia von 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
Stephan P. Rosshart
author_facet Solveig Runge
Silvia von 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
Stephan P. Rosshart
author_sort Solveig Runge
collection DOAJ
description 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.
format Article
id doaj-art-84928e2da09e4d519a4cfed9c90f7ed8
institution OA Journals
issn 2041-1723
language English
publishDate 2025-06-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-84928e2da09e4d519a4cfed9c90f7ed82025-08-20T02:06:36ZengNature PortfolioNature Communications2041-17232025-06-0116111410.1038/s41467-025-60554-2Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotypeSolveig Runge0Silvia von Zedtwitz1Alexander M. Maucher2Philipp Bruno3Lisa Osbelt4Bei Zhao5Anne M. Gernand6Till R. Lesker7Katja Gräwe8Manuel Rogg9Christoph Schell10Melanie Boerries11Till Strowig12Geoffroy Andrieux13Benedikt Hild14Stephan P. Rosshart15Department of Microbiome Research, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)Department of Medicine II, Medical Center - University of Freiburg, Faculty of MedicineDepartment of Medicine II, Medical Center - University of Freiburg, Faculty of MedicineDepartment of Microbiome Research, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)Department of Microbial Immune Regulation, Helmholtz Center for Infection ResearchDepartment of Medicine II, Medical Center - University of Freiburg, Faculty of MedicineDepartment of Medicine II, Medical Center - University of Freiburg, Faculty of MedicineDepartment of Microbial Immune Regulation, Helmholtz Center for Infection ResearchInstitute of Surgical Pathology, Medical Center - University of Freiburg, Faculty of MedicineInstitute of Surgical Pathology, Medical Center - University of Freiburg, Faculty of MedicineInstitute of Surgical Pathology, Medical Center - University of Freiburg, Faculty of MedicineInstitute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Microbial Immune Regulation, Helmholtz Center for Infection ResearchInstitute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-EssenDepartment of Microbiome Research, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)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.https://doi.org/10.1038/s41467-025-60554-2
spellingShingle Solveig Runge
Silvia von 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
Stephan P. Rosshart
Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
Nature Communications
title Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
title_full Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
title_fullStr Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
title_full_unstemmed Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
title_short Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
title_sort laboratory mice engrafted with natural gut microbiota possess a wildling like phenotype
url https://doi.org/10.1038/s41467-025-60554-2
work_keys_str_mv AT solveigrunge laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT silviavonzedtwitz laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT alexandermmaucher laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT philippbruno laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT lisaosbelt laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT beizhao laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT annemgernand laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT tillrlesker laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT katjagrawe laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT manuelrogg laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT christophschell laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT melanieboerries laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT tillstrowig laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT geoffroyandrieux laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT benedikthild laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype
AT stephanprosshart laboratorymiceengraftedwithnaturalgutmicrobiotapossessawildlinglikephenotype