Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis

Forster, S. C. et al. (2022) Identification of gut microbial species linked with disease variability in a widely used mouse model of colitis. Nature Microbiology, 7(4), pp. 590-599. (doi: 10.1038/s41564-022-01094-z) (PMID:35365791) (PMCID:PMC8975739)

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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.

Item Type:Articles
Additional Information:This work was supported by the Wellcome Trust (no. 098051), the Australian National Health and Medical Research Council (nos. 1091097, 1159239 and 1141564 to S.C.F.) and the Victorian Government’s Operational Infrastructure Support Program (S.C.F.). V.A.P. is supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (no. 206245/Z/17/Z). B.S.B.-J. is supported by a studentship from the Rosetrees Trust (no. A2194). K.J.M. is supported by a Wellcome Trust Investigator Award (no. 102972/Z/13/Z).
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Forster, S. C., Clare, S., Beresford-Jones, B. S., Harcourt, K., Notley, G., Stares, M. D., Kumar, N., Soderholm, A. T., Adoum, A., Wong, H., Morón, B., Brandt, C., Dougan, G., Adams, D. J., Maloy, K. J., Pedicord, V. A., and Lawley, T. D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Nature Microbiology
Publisher:Nature Research
ISSN (Online):2058-5276
Published Online:01 April 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Nature Microbiology 7(4):590-599
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
313264Regulation of intestinal immune homeostasis by NOD-like receptorsKevin MaloyWellcome Trust (WELLCOTR)102972/A/13/ZIII - Immunology