Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis.
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Authors
Clare, Simon
Beresford-Jones, Benjamin S
Harcourt, Katherine
Notley, George
Stares, Mark D
Soderholm, Amelia T
Adoum, Anne
Brandt, Cordelia
Maloy, Kevin J
Publication Date
2022-04Journal Title
Nat Microbiol
ISSN
2058-5276
Publisher
Springer Science and Business Media LLC
Volume
7
Issue
4
Pages
590-599
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Forster, S. C., Clare, S., Beresford-Jones, B. S., Harcourt, K., Notley, G., Stares, M. D., Kumar, N., et al. (2022). Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis.. Nat Microbiol, 7 (4), 590-599. https://doi.org/10.1038/s41564-022-01094-z
Abstract
Experimental mouse models are central to basic biomedical research; however, variability exists across genetically identical mice and mouse facilities making comparisons difficult. Whether specific indigenous gut bacteria drive immunophenotypic variability in mouse models of human disease remains poorly understood. We performed a large-scale experiment using 579 genetically identical laboratory mice from a single animal facility, designed to identify the causes of disease variability in the widely used dextran sulphate sodium mouse model of inflammatory bowel disease. Commonly used treatment endpoint measures-weight loss and intestinal pathology-showed limited correlation and varied across mouse lineages. Analysis of the gut microbiome, coupled with machine learning and targeted anaerobic culturing, identified and isolated two previously undescribed species, Duncaniella muricolitica and Alistipes okayasuensis, and demonstrated that they exert dominant effects in the dextran sulphate sodium model leading to variable treatment endpoint measures. We show that the identified gut microbial species are common, but not ubiquitous, in mouse facilities around the world, and suggest that researchers monitor for these species to provide experimental design opportunities for improved mouse models of human intestinal diseases.
Keywords
Animals, Mice, Bacteroidetes, Colitis, Inflammatory Bowel Diseases, Disease Models, Animal, Gastrointestinal Microbiome
Sponsorship
Wellcome Trust (206245/Z/17/Z)
Wellcome Trust (206245/A/17/Z)
Identifiers
35365791, PMC8975739
External DOI: https://doi.org/10.1038/s41564-022-01094-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336815
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