The Mouse Gastrointestinal Bacteria Catalogue enables translation between the mouse and human gut microbiotas via functional mapping

Benjamin S Beresford-Jones,Samuel C Forster,Mark D Stares,George Notley,Elisa Viciani,Hilary P Browne,Daniel J Boehmler,Amelia T Soderholm,Nitin Kumar,Kevin Vervier,Justin R Cross,Alexandre Almeida,Trevor D Lawley,Virginia A Pedicord

doi:10.1016/j.chom.2021.12.003

Abstract

SummaryHuman health and disease have increasingly been shown to be impacted by the gut microbiota, and mouse models are essential for investigating these effects. However, the compositions of human and mouse gut microbiotas are distinct, limiting translation of microbiota research between these hosts. To address this, we constructed the Mouse Gastrointestinal Bacteria Catalogue (MGBC), a repository of 26,640 high-quality mouse microbiota-derived bacterial genomes. This catalog enables species-level analyses for mapping functions of interest and identifying functionally equivalent taxa between the microbiotas of humans and mice. We have complemented this with a publicly deposited collection of 223 bacterial isolates, including 62 previously uncultured species, to facilitate experimental investigation of individual commensal bacteria functions in vitro and in vivo. Together, these resources provide the ability to identify and test functionally equivalent members of the host-specific gut microbiotas of humans and mice and support the informed use of mouse models in human microbiota research.

Highlights

The mammalian gastrointestinal tract hosts trillions of bacteria, known as the gut microbiota, that actively impact the health of the host
Bacterial culturing and isolate biobanking are essential for research and biotechnology applications by enabling the validation of in silico findings and investigation of underlying biological mechanisms
10,000 isolate genomes exist for humanderived commensal bacteria (Almeida et al, 2021; Poyet et al, 2019), but fewer than 400 have been published for the mouse

Summary

Introduction

The mammalian gastrointestinal tract hosts trillions of bacteria, known as the gut microbiota, that actively impact the health of the host. Variations in this bacterial ecosystem are associated with susceptibility to and outcomes of many human diseases (Armour et al, 2019), from adverse nutritional states In order to characterize these microbial associations for therapeutic benefit, it is necessary to establish causal relationships between microbial factors and phenotypes (Neville et al, 2018) To this end, mouse models are essential tools in microbiota research, allowing controlled experimental studies in a physiologically and genetically tractable system. While it has been reported that the microbiotas of humans and mice are functionally comparable (Liu et al, 2020; Xiao et al, 2015), mice treated with a human microbiota exhibit compromised immune maturation and performance compared with mice harboring a mouse-derived microbiota (Chung et al, 2012; Lundberg et al, 2020), resulting in differences in susceptibility to infectious (Chung et al, 2012)

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