Maternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Composition

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dc.contributor.authorRingel-Scaia, Veronica M.en
dc.contributor.authorQin, Yufengen
dc.contributor.authorThomas, Cassidy A.en
dc.contributor.authorHuie, Kathleen E.en
dc.contributor.authorMcDaniel, Dylan K.en
dc.contributor.authorEden, Kristinen
dc.contributor.authorWade, Paul A.en
dc.contributor.authorAllen, Irving C.en
dc.date.accessioned2019-08-30T13:47:05Zen
dc.date.available2019-08-30T13:47:05Zen
dc.date.issued2019-02-13en
dc.description.abstractThe NLRP1 inflammasome attenuates inflammatory bowel disease (IBD) progression and colitis-associated tumorigenesis. A possible mechanism postulates that the lack of the NLRP1 inflammasome creates permissive niches in the gut for pathogenic bacteria to flourish, causing dysbiosis and increased IBD susceptibility. To evaluate this hypothesis, we characterized the gut microbiome of wild-type, Nlrp1b-/-, and Asc-/- mice under naive conditions by sequencing the V3 region of the 16s rRNA gene. For both genetically modified mouse lines, the microbiome composition reflected overrepresentation of bacteria associated with dysbiosis relative to wild-type animals. Measurement of short- and medium-chain fatty acids by mass spectrometry further revealed significant differences between genotypes. However, prior to concluding that the NLRP1 inflammasome plays a role in regulating the composition of the microbiome, we evaluated two additional strategies for cohousing wild-type and Nlrp1b-/- mice: breeding homozygous parents and cohousing at weaning, and breeding from heterozygous parents and cohousing littermates. We found that maternal influence was the greater predictor of microbiome composition rather than genotype. With the rise in microbiome research across disciplines, our study should be viewed as a cautionary example that illustrates the importance of careful breeding and housing strategies when evaluating host-microbiome interactions. (C) 2019 The Author(s) Published by S. Karger AG, Baselen
dc.description.notesGrants were awarded from the US National Institutes of Health (I.C.A.; R03 DK105975 and K01 DK092355); the Via College of Osteopathic Medicine (VCOM) One Health Center Seed Funding (I.C.A.); Virginia Maryland College of Veterinary Medicine Internal Research Competition (I.C.A.), and the Virginia Tech Institute for Critical Technology and Applied Sciences (I.C.A.). V.M.R.-S. was supported through the American Association of Immunologists Careers in Immunology Fellowship Program. This work was supported, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences (ES101965 to P.A.W.).en
dc.description.sponsorshipUS National Institutes of Health [R03 DK105975, K01 DK092355]; Via College of Osteopathic Medicine (VCOM) One Health Center Seed Funding; Virginia Maryland College of Veterinary Medicine Internal Research Competition; Virginia Tech Institute for Critical Technology and Applied Sciences; American Association of Immunologists Careers in Immunology Fellowship Program; Intramural Research Program of the National Institute of Environmental Health Sciences [ES101965]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1159/000495850en
dc.identifier.eissn1662-8128en
dc.identifier.issn1662-811Xen
dc.identifier.issue5en
dc.identifier.pmid30759441en
dc.identifier.urihttp://hdl.handle.net/10919/93320en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectNod-like receptoren
dc.subjectMicrobiomeen
dc.subjectInflammatory bowel diseaseen
dc.subjectExperimental colitisen
dc.subjectColitis-associated canceren
dc.subjectShort-chain fatty aciden
dc.subjectASCen
dc.subjectDysbiosisen
dc.titleMaternal Influence and Murine Housing Confound Impact of NLRP1 Inflammasome on Microbiome Compositionen
dc.title.serialJournal of Innate Immunityen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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