Analysis of metagenome-assembled genomes from the mouse gut microbiota reveals distinctive strain-level characteristics

Abstract

21The laboratorial mouse harbors a unique gut microbiota with potential value for human microbiota-22 associated studies. Mouse gut microbiota has been explored at the genus and species levels, but features 23 rarely been showed at the strain level. The identification of 833,051 and 658,438 nonredundant genes of 24 faeces and gut content samples from the laboratorial C57/BL mice showed over half of these genes were 25 newly found compared to the previous mouse gut microbial gene catalogue. Metagenome-assembled 26 genomes (MAGs) was used to reconstruct 46 nonredundant MAGs belonging to uncultured specieses. These 27MAGs included members across all phyla in mouse gut (i.e. Firmicutes, Bacteroidetes, Proteobacteria, 28 Deferribacteres, Verrucomicrobia, and Tenericutes) and allowed a strain-level delineating of the mouse gut 29 microbiota. Comparison of MAGs with human gut colonies revealed distinctive genomic and functional 30 characteristics of mouse's Bacteroidetes and Firmicutes strains. Genomic characteristics of rare phyla in 31 mouse gut microbiota were demonstrated by MAG approach, including strains of Mucispirillum schaedleri, 32Parasutterella excrementihominis, Helicobacter typhlonius, and Akkermansia muciniphila. 33 Importance 34 The identification of nonredundant genes suggested the existence of unknown microbes in the mouse gut 35 samples. The metagenome-assembled genomes (MAGs) instantiated the specificity of mouse gut species and 36 revealed an intestinal microbial correlation between mouse and human. The cultivation of faeces and gut 37 contents sample validated the existence of MAGs and estimate their accuracy. Full-length 16S ribosomal 38 RNA gene sequencing enabled taxonomic characterization. This study highlighted a unique ecosystem in the 39 gut of laboratorial mice that obviously differed with the human gut flora at the strain level. The outcomes 40 may be beneficial to researches based on laboratorial mouse models. 41 42 Introduction 43The gut microbiota is a dense and diverse ecosystem (1). The associations between altered gut microbial 44 composition and various pathogenesis, such as obesity (2, 3), type 2 diabetes (4), rheumatoid arthritis (5), 45 and allergy (6), has become a research hotspot. Murine models, especially mouse, are widely used in 46 biomedical study. Many studies have showed that mouse intestinal models also play a pivotal role in human 47 gut microbial research. Some phyla in mouse intestinal flora, such as Firmicutes, Bacteroidetes, 48Proteobacteria, has resemblances with that in human (7, 8). In addition, there are plenty of similarities in 49 anatomy, genetics and physiology between mouse and human (9). These features make the mouse one of the 50 most essential model animals in laboratory. However, mouse gut microbiota could be influenced by many 51 factors, including diet, ambient temperature and cleanliness. Hence, there are still some distinctions between 52 human and mouse gut microbiota. Previous studies have showed that over 50% of genera in mouse gut 53 microbi...

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

“…Recent studies have estimated a taxonomic overlap of 4-5% between human and mouse hosts 9,10 , but it is unknown which species are shared and whether these estimates are accurate at the genome level. Comparing functional annotations of human and mouse metagenomes has yielded estimates of up to 95% functional crossover 9 ; however, the taxonomic locations of these functions are not known nor their implications for medical and pharmaceutical research.…”