Wild microbes make lab mice more accurate models for human immune studies

2019

Challenge

Laboratory mice have long been the go-to model for understanding biologic processes, producing insights that can then be applied to humans. However, they do have limitations. For example, recent studies have shown that conventional laboratory mice are too far removed from natural environmental conditions to have developed the complex community of microbes living in their bodies, called the microbiome, that is needed to predict the complex immune responses of humans. Mammals and their immune systems evolved to survive and thrive in a microbial world and behave differently in a sanitized environment.

Advance

Based on the idea that natural microbes co-evolved with the animals they inhabit, IRP researchers led by senior investigator Barbara Rehermann, M.D., created mouse models that combine the natural microbiome of wild mice with the controllable genetics of laboratory mice. The wild mouse microbiome was maintained over multiple generations of these mice, outcompeted microbes living in laboratory mice in co-housing experiments, and demonstrated resilience to environmental challenges. Finally, two preclinical studies showed that mice whose bodies harbored infectious pathogens and a microbiome resembling that of wild mice exhibited immune responses that closely resembled typical human immune responses, while conventional laboratory mice did not.

Impact

A mouse model that includes natural microbes and pathogens may lead to the discovery of biological mechanisms that take place in the natural world, but not in the laboratory. In addition, it may improve scientists’ ability to reproduce the results of animal research in human studies and increase the bench-to-bedside safety and success of immunological studies.

Publications

Rosshart SP, Herz J, Vassallo BG, Hunter A, Wall MK, Badger JH, McCulloch JA, Anastasakis DG, Sarshad AA, Leonardi I, Collins N, Blatter JA, Han SJ, Tamoutounour S, Potapova S, Foster St Claire MB, Yuan W, Sen SK, Dreier MS, Hild B, Hafner M, Wang D, Iliev ID, Belkaid Y, Trinchieri G, Rehermann B (2019). Laboratory mice born to wild mice have natural microbiota and model human immune responses. Science. 365(6452).

Rosshart SP, Vassallo BG, Angeletti D, Hutchinson DS, Morgan AP, Takeda K, Hickman HD, McCulloch JA, Badger JH, Ajami NJ, Trinchieri G, Pardo-Manuel de Villena F, Yewdell JW, Rehermann B (2017). Wild mouse gut microbiota promotes host fitness and improves disease resistance. Cell. 171(5):1015-1028.