A new investigatory mouse model—designed to have a microbiome that is similar to that of wild mice—has been shown to be a potentially better predictor of human response to certain drugs than the more commonly used lab mice. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) study authors repeated two preclinical studies which both demonstrated positive results in mice but went on to fail during verification in the human testing model.
This is actually a common hurdle encountered during drug testing: that mice models show promise but fail in human models. Scientist are beginning to understand certain characteristics—genetics and physiology, mostly—influence the outcome of the testing. And at the core of these characteristics, researchers have learned, environmental factors like microbiome might have the biggest influence of all.
The new model using wild mice, however, showed more consistency with human models, giving researchers a new angle for overcoming these hurdles. According to senior study author Barbara Rehermann, MD, “We wanted to create a mouse model that better resembles a mouse you’d find in the wild.”
The chief of the NIDDK Liver Diseases Branch Immunology Section goes on to say, “Our rationale was that the immune responses and microbiota of wild mice and humans are likely shaped in a similar way—through contact with diverse microbes out in the real world.”
Most of the time, preclinical research would use inbred mice with specific gene expression that were raised in sterile environments. NIDDK postdoctoral fellow Stephan Rosshart, MD, advises that this would be comparable to a human being isolated in an entirely sterile condition from birth all the way to adulthood, never getting any type of infection the entire time. That, of course, would never occur: but if it did, it would certainly distort normal human immune response.
These ideas have populated human health for quite a long time: that exposure to the environment contributes to a diverse microbiome that improves immunity. As such, the co-lead study author notes, “A healthy microbiome is important not only for the immune system, but also for digestion, metabolism, even the brain. The wilding model could help us better understand what causes diseases, and what can protect us from them, thus benefiting many areas of biomedical research.”