One fecal pellet to rule them all

Introduction: 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.

Aim: We aim to present a robust, feasible and standardizable approach for transplanting natural gut microbiota from wildlings into laboratory mice.

Methods: Laboratory mice were exposed to a defined amount of natural microbiota and their immune status, metabolite production and their disease response were tested 28 days later.

Results: 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. TXwildlings displayed similiar response to a disease challenge was mice with a natural microbiota did. Furthermore, we were able to quickly and completely change the microbiota composition of laboratory mice through only a single gavage without prior treatment of the reciepient mice.

Conclusion: 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.

Publication History

Article published online:
04 September 2025