Mouse models are essential for biomedical science and drug discovery, yet it is not known how the bacteria in the mouse microbiota -- important determinants of phenotypes of health and disease -- affect their relevance to human disease. To interrogate the taxonomic and functional differences between the human and mouse gut microbiotas, we developed the Mouse Microbial Genome Collection (MMGC), a compilation of 276 genomes from cultured isolates and 45,218 metagenome-assembled genomes (MAGs) from 1,960 publicly available mouse metagenomes. The MMGC reveals that while only 2.65% of bacterial species are shared between mouse and human, over 80% of annotatable functions are present in both microbiomes. Using drug metabolism and butyrate synthesis as examples, we illustrate that although the species harbouring these key functions can differ between hosts, the MMGC enables identification of functionally equivalent taxa in the mouse and human microbiotas. The MMGC thereby facilitates the informed use of mice in biomedical research by providing access to the conservation and taxonomic locations of bacterial functions of interest.

42Gastrointestinal microbiota and immune cells interact closely and display regional 43 specificity, but little is known about how these communities differ with location. Here, 44we simultaneously assess microbiota and single immune cells across the healthy, 45 adult human colon, with paired characterisation of immune cells in the mesenteric 46 lymph nodes, to delineate colonic immune niches at steady-state. We describe 47 distinct T helper cell activation and migration profiles along the colon and 48 characterise the transcriptional adaptation trajectory of T regulatory cells between 49 lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal 50 expansion and mutational frequency from caecum to sigmoid colon, and link this to 51 the increasing number of reactive bacterial species. 52 53