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A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System
Published on: August 30, 2019
Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype
Solveig Runge1,2,3, Silvia von Zedtwitz4, Alexander M Maucher4,5
1Department of Microbiome Research, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. Solveig.Runge@uk-erlangen.de.
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.
Insights
Introducing wild mouse gut microbiota into lab mice improves research reproducibility. This approach enhances the mouse model
Area of Science:
- Microbiology
- Immunology
- Animal Models
Background:
- Conventional laboratory mice under specific pathogen-free (SPF) conditions are standard research models.
- Irreproducibility in rodent studies is increasing, questioning the suitability of SPF mice.
- Variability in SPF microbiota is a key factor contributing to inconsistent research data.
Purpose of the Study:
- To develop a standardizable method for transferring wild mouse gut microbiota to laboratory mice.
- To improve the structural and functional resemblance of laboratory mouse microbiota to that of wild mammals.
- To enhance the host physiology and immune system maturation in laboratory mice.
Main Methods:
- A robust and feasible method for transplanting gut microbiota from wild rodents into laboratory mice was developed.
- The engraftment process was monitored to ensure successful transfer and colonization of wild-type microbiota.
- Physiological and immunological changes in recipient mice were assessed post-transplantation.
Main Results:
- Transplanted mice (TXwildlings) successfully adopted a wildling-like gut microbiota structure and function.
- Host physiology shifted towards a more mature immune system profile.
- The developed microbiota exhibited characteristics similar to those observed in adult humans.
Conclusions:
- Wild mouse-derived microbiota can be standardized and transplanted into laboratory mice.
- This approach enhances the biological relevance of mouse models for biomedical research.
- Adopting wild-type microbiota standards is anticipated to improve the reproducibility and generalizability of research findings.
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