Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility

Experimental reproducibility in mouse models is impacted by both genetics and environment. The generation of reproducible data is critical for the biomedical enterprise and has become a major concern for the scientific community and funding agencies alike. Among the factors that impact reproducibility is that the murine microbiome varies across vendors, time and multiple other factors. How the microbiome might change over time within a vendor has not been clearly assessed. We observed a profound and lasting change in the severity of malaria in mice obtained within a span of three months from one commercial vendor. Gut microbiota analysis identified a distinct and lasting shift in bacteria populations in mice obtained over time within a specific production suite from the vendor that affected the reproducibility of infectious disease and cancer model systems. Germ-free mice colonized with cecal microbiota from mice within the same production suite before and after this change followed by Plasmodium infection provided a direct demonstration that the change in gut microbiota profoundly impacted the severity of malaria. Moreover, these changes altered acute bacterial burden following Salmonella infection, and altered tumor burden in a lung tumorigenesis model. These changes in gut bacteria may have impacted the experimental reproducibility of diverse research groups, and highlights the need for both laboratory animal providers and researchers to collaborate in determining the methods and criteria needed to stabilize the gut microbiota of animal breeding colonies and research cohorts, and to develop a microbiome solution to increase experimental rigor and reproducibility.