Dominant effects of the immediate environment on the gut microbiome of mice used in biomedical research

Abstract

There are concerns regarding the reproducibility and predictive value of mouse models of human disease. Notwithstanding those legitimate concerns, genetically engineered mouse (GEM) models provide an invaluable platform to investigate gene function or effects of environmental factors in a biological system. The microbiome of GEM models significantly influences model phenotypes and thus represents a possible source of poor reproducibility. While the microbiome is often incorporated in research investigating disease mechanisms using GEMs, limited information is available regarding the similarity of the microbiome of GEM models within and between research labs at the same institution, or across institutions. Moreover, while the microbiome of founder mice from different suppliers is known to differ, the degree to which features present in supplier-origin microbiomes are retained in GEM colonies throughout experimentation is unclear. These data demonstrate the robust effect of lab-level environment and the need for sample collection concurrent with phenotyping.