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

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cam.issuedOnline2022-04
dc.contributor.authorForster, Samuel C
dc.contributor.authorClare, Simon
dc.contributor.authorBeresford-Jones, Benjamin S
dc.contributor.authorHarcourt, Katherine
dc.contributor.authorNotley, George
dc.contributor.authorStares, Mark D
dc.contributor.authorKumar, Nitin
dc.contributor.authorSoderholm, Amelia T
dc.contributor.authorAdoum, Anne
dc.contributor.authorWong, Hannah
dc.contributor.authorMorón, Bélen
dc.contributor.authorBrandt, Cordelia
dc.contributor.authorDougan, Gordon
dc.contributor.authorAdams, David J
dc.contributor.authorMaloy, Kevin J
dc.contributor.authorPedicord, Virginia A
dc.contributor.authorLawley, Trevor D
dc.contributor.orcidForster, Samuel C [0000-0003-4144-2537]
dc.contributor.orcidKumar, Nitin [0000-0002-2140-4923]
dc.contributor.orcidWong, Hannah [0000-0002-9530-7106]
dc.contributor.orcidMorón, Bélen [0000-0003-4815-7536]
dc.contributor.orcidAdams, David J [0000-0001-9490-0306]
dc.contributor.orcidPedicord, Virginia A [0000-0001-9625-3122]
dc.contributor.orcidLawley, Trevor D [0000-0002-4805-621X]
dc.date.accessioned2022-06-14T16:00:29Z
dc.date.available2022-06-14T16:00:29Z
dc.date.issued2022-04
dc.date.submitted2021-03-02
dc.date.updated2022-06-14T16:00:29Z
dc.description.abstractExperimental 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.
dc.identifier.doi10.17863/CAM.85494
dc.identifier.eissn2058-5276
dc.identifier.issn2058-5276
dc.identifier.others41564-022-01094-z
dc.identifier.other1094
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338085
dc.languageen
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41564-022-01094-z
dc.subjectAnimals
dc.subjectBacteroidetes
dc.subjectColitis
dc.subjectDisease Models, Animal
dc.subjectGastrointestinal Microbiome
dc.subjectInflammatory Bowel Diseases
dc.subjectMice
dc.titleIdentification of gut microbial species linked with disease variability in a widely used mouse model of colitis.
dc.typeArticle
dcterms.dateAccepted2022-02-24
prism.endingPage599
prism.issueIdentifier4
prism.publicationNameNat Microbiol
prism.startingPage590
prism.volume7
pubs.funder-project-idWellcome Trust (206245/Z/17/Z)
pubs.funder-project-idWellcome Trust (206245/A/17/Z)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41564-022-01094-z

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