Modeling a Superorganism - Considerations Regarding the Use of "Dirty" Mice in Biomedical Research

An ever-expanding body of evidence in both humans and animal models demonstrates the influence of the resident gut microbiota on host health and disease susceptibility. However, as unwanted bacterial, viral, protozoal, and parasitic agents have gradually been eliminated from colonies of purpose-bred laboratory mice, the resident microbiota has lost richness and complexity. Recent studies have shown that the ultra-hygienic environment of traditional laboratory mice and lack of antigenic exposure during development results in mice with an immune system more akin to that of a neonate than an adult human. In contrast, wild mice or mice purchased from pet stores are exposed to much greater antigen burdens and their immune system reflects this with significantly greater numbers of memory T cells and more robust vaccine responses. The current review explores the use of alternative sources for research rodents, with an emphasis on the differences in resident gut microbiota and pathogen burden between wild mice, pet store-origin mice, and traditional laboratory mice. Specifically, the literature is compared and contrasted to our own data reflecting the endogenous gut microbiota and pathogen load of wild and pet store mice, as well as the changes in both during and after procedures intended to eliminate certain zoonotic agents present in pet store mice. These data demonstrate that, while alternative sources of research rodents will likely provide models that are more translatable to the human condition, there are also several real-world considerations for scientists including contamination of research facilities and human health risks such as zoonotic diseases.