Deeper Comparison Of The Human And Mouse Microbiota Reveals The Utility Of Mouse Models

Abstract Mouse models are the backbone of many immunological studies and understanding their relevance to human disease is critical when interpreting results and moving research into the clinic. The intestinal microbiota performs essential roles in host physiology including immune development and metabolic encoding. However, it is currently uncertain to what degree the microbiota of mice is taxonomically and functionally comparable to humans. In addition, the microbiota has been identified as a leading cause of irreproducibility in mouse models but current mouse commensal genome databases are inadequate to define the microbes responsible. Better characterization of the mouse microbiota is therefore necessary to understand the relevance of mouse studies to human medicine, as well as produce cleaner, more reproducible science. We performed high-throughput culturing and whole-genome sequencing of commensals from the faeces of specific pathogen-free mice. These genomes represent hundreds of novel species with which we define the taxonomic and functional relatedness of the mouse and human microbiota. We highlight functional pathways that are common and unique to each host species, thus describing areas of study where mouse models may be used validly. We also demonstrate the requirement for mouse commensal-specific databases for analysis of mouse samples. Our work brings a new level of understanding to the mouse microbiota. By supplying an extensive selection of mouse commensal genomes, we facilitate comparison of the microbiota of mice, not only providing a means to understand issues of irreproducibility in mouse research but also delivering new opportunities to correlate and validate specific commensals with phenotypes of interest.