Laboratory mice have been bred for around a century originating from house mice and raised through generations of sibling mating. This has resulted in mice with nearly identical genetics allowing researchers to attribute any experimental differences to the tested conditions rather than genetic variation. This makes them ideal for addressing medical research questions explains Prof. Dr. Stephan Rosshart Professor of Microbiomics at FAU and head of Microbiomics Research at Universitätsklinikum Erlangen (UKER).

To minimize external influences lab mice are typically raised in highly sterile environments. However this practice comes with two key drawbacks: the mice fail to develop a mature immune system and their immune responses differ significantly from those of wild mice and humans. As a result findings from such experiments may not translate well to human studies treatments effective in lab mice often fail in clinical trials.

The second major drawback involves the microbiome the community of microorganisms living on the skin in the mouth and throughout the digestive tract of mice. Because lab mice are exposed to a very limited range of bacteria their microbiomes differ greatly from those of wild mice and are highly sensitive. Even slight changes in housing conditions can significantly shift the microbial composition explains Prof. Rosshart.

As a result mice kept in two different labs even within the same city can develop entirely different microbiomes potentially impacting experimental outcomes. This variability is believed to contribute to the so-called reproducibility crisis where results observed in one lab cannot be replicated by others.

In 2019 while working in the U.S., Prof. Rosshart developed wildlings by using house mice as surrogates and implanting them with lab mouse embryos. These offspring developed microbiomes similar to wild mice and possessed immune systems more comparable to those of humans making experimental data more relevant for human biology. In the current study Rosshart and his team at Erlangen have simplified and standardized this process to address the reproducibility crisis in research.

We isolated microorganisms from a wildling’s gastrointestinal tract and transferred them via a tube into the stomach of a standard lab mouse Rosshart explains. Remarkably not only did that mouse develop a wild-like microbiome within days but so did the four cage-mates it lived with. The resulting microbiome proved highly stable unsurprising given its evolutionary refinement. Researchers found that wild mice from geographically distant regions like the U.S. and Germany carry nearly identical microbiomes.

The transplantation also triggered maturation of the mice’s immune systems aligning them more closely with those of wild mice and adult humans. This could enable more realistic and translatable experimental outcomes compared to results from animals raised in sterile environments. We can freeze this wild-derived microbiome and ship it globally says Rosshart. It allows labs to easily introduce these bacteria to many mice potentially establishing a standardized microbiome that boosts reproducibility and the overall reliability of biomedical research.

Source: https://www.fau.eu/2025/06/news/new-approach-to-boost-reliability-of-findings-from-animal-experiments/