Functional and taxonomic comparison of mouse and human gut microbiotas using extensive culturing and metagenomics

Abstract

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.

A mouse model of occult intestinal colonization demonstrating antibiotic-induced outgrowth of carbapenem-resistantEnterobacteriaceae

“…This suggests that during ampicillin treatment, xylose may be compensated for by other carbon sources, such as fucose or sialic acid [42,57], thus allowing outgrowth regardless of xylose availability. Moreover, the microbiome of mouse and human have considerable differences [58], hence further work is needed to confirm whether our findings on mouse microbiome extend to human microbiome.…”

MRGM: a mouse reference gut microbiome reveals a large functional discrepancy for gut bacteria of the same genus between mice and humans

“…MAGs and isolated genomes from several public databases that included iMGMC (15), MMGC (26), miBC (12), mGMB (13), and PATRIC (27). The quality of MAGs is conventionally evaluated based on their completeness and contamination of redundant and overlapping genomic fragments according to CheckM (25).…”

“…We used Kraken2 to compare the taxonomic classification of sequencing reads across different prokaryotic genome databases, including RefSeq-based standard database and custom databases constructed from the genomes of iMGMC (15), MRGM, and HRGM (10). We also included a recently released public Kraken2 database from MMGC (26). We assessed the taxonomic classification rate using 86 WMS samples according to single-end sequencing from PRJEB37572 (44) and 30 WMS samples by pairedend sequencing from PRJNA730805 (45) that were not used for the construction of any of the genome catalogs.…”

Gut Microbiota and Host Metabolism: From Proof of Concept to Therapeutic Intervention

“…However, the gut microbiota is dominated by mainly two phyla: Firmicutes and Bacteroidetes, representing approximatively 85-90% of the total microbiota, whereas Actinobacteria, Proteobacteria and Verrucomicrobia are frequent, but generally minor constituents [5][6][7]. Interestingly, even though the gut microbiota composition of an individual is as unique as a fingerprint, the metabolic functions are remarkably conserved between individuals [8] and even between humans and other animal species [9]. Metagenomic analysis showed that 40% of the gut microbial gene pool is shared among all individuals around the world.…”