Abstract

Mouse is the most used model for studying the impact of microbiota on its host, but the repertoire of species from the mouse gut microbiome remains largely unknown. Accordingly, the similarity between human and mouse microbiomes at a low taxonomic level is not clear. We construct a comprehensive mouse microbiota genome (CMMG) catalog by assembling all currently available mouse gut metagenomes and combining them with published reference and metagenome-assembled genomes. The 41’798 genomes cluster into 1’573 species, of which 78.1% are uncultured, and we discovered 226 new genera, seven new families, and one new order. CMMG enables an unprecedented coverage of the mouse gut microbiome exceeding 86%, increases the mapping rate over four-fold, and allows functional microbiota analyses of human and mouse linking them to the driver species. Comparing CMMG to microbiota from the unified human gastrointestinal genomes shows an overlap of 62% at the genus but only 10% at the species level, demonstrating that human and mouse gut microbiota are largely distinct. CMMG contains the most comprehensive collection of consistently functionally annotated species of the mouse and human microbiome to date, setting the ground for analysis of new and reanalysis of existing datasets at an unprecedented depth.

Highlights

  • Mouse is the most used model for studying the microbiota importance due to several factors: availability of samples from different parts of the gastrointestinal tract, treatment options, controlled housing environment and diet, defined genetic background, and ethical considerations

  • We created a comprehensive catalog of all bacterial species commonly living in the gut of laboratory mice by analyzing all publicly available metagenomes from the mouse gut

  • The integrated mouse gut metagenomic catalog [10] increased the fraction of reads mapped to genes compared to the MGC v1

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Summary

Introduction

Mouse is the most used model for studying the microbiota importance due to several factors: availability of samples from different parts of the gastrointestinal tract, treatment options, controlled housing environment and diet, defined genetic background, and ethical considerations. Most mouse microbiome studies are performed by sequencing 16S variable regions, sometimes mislabeled as metagenomics While this technique has allowed a general overview of the microbiota bacterial taxonomic diversity down to the genus level, it is not suited for identifying species for most organisms [1]. Previous efforts led to the creation of a gene catalog of the mouse metagenome (MGC v1) [3], by sequencing fecal samples from mice with different genotypes and housed in different conditions. This catalog enables projecting known functional annotations of genes and allows up to 50% mapping rate of fecal shotgun sequences. Lesker et al generated a set of 13,619 mousespecific MAGs (mMAG) not integrated into the iMGMC, which was made available for further studies

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