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dc.contributor.authorMorgan, Xochitl Cen_US
dc.contributor.authorKabakchiev, Boykoen_US
dc.contributor.authorWaldron, Levien_US
dc.contributor.authorTyler, Andrea Den_US
dc.contributor.authorTickle, Timothy Len_US
dc.contributor.authorMilgrom, Raquelen_US
dc.contributor.authorStempak, Joanne Men_US
dc.contributor.authorGevers, Dirken_US
dc.contributor.authorXavier, Ramnik Jen_US
dc.contributor.authorSilverberg, Mark Sen_US
dc.contributor.authorHuttenhower, Curtisen_US
dc.date.accessioned2015-05-04T15:26:12Z
dc.date.issued2015en_US
dc.identifier.citationMorgan, X. C., B. Kabakchiev, L. Waldron, A. D. Tyler, T. L. Tickle, R. Milgrom, J. M. Stempak, et al. 2015. “Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.” Genome Biology 16 (1): 67. doi:10.1186/s13059-015-0637-x. http://dx.doi.org/10.1186/s13059-015-0637-x.en
dc.identifier.issn1465-6906en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:15034823
dc.description.abstractBackground: Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze host transcriptomic data and 16S rRNA gene sequencing data from paired biopsies from IPAA patients with UC and familial adenomatous polyposis. To achieve power for a genome-wide microbiome-transcriptome association study, we use principal component analysis for transcript and clade reduction, and identify significant co-variation between clades and transcripts. Results: Host transcripts co-vary primarily with biopsy location and inflammation, while microbes co-vary primarily with antibiotic use. Transcript-microbe associations are surprisingly modest, but the most strongly microbially-associated host transcript pattern is enriched for complement cascade genes and for the interleukin-12 pathway. Activation of these host processes is inversely correlated with Sutterella, Akkermansia, Bifidobacteria, and Roseburia abundance, and positively correlated with Escherichia abundance. Conclusions: This study quantifies the effects of inflammation, antibiotic use, and biopsy location upon the microbiome and host transcriptome during pouchitis. Understanding these effects is essential for basic biological insights as well as for well-designed and adequately-powered studies. Additionally, our study provides a method for profiling host-microbe interactions with appropriate statistical power using high-throughput sequencing, and suggests that cross-sectional changes in gut epithelial transcription are not a major component of the host-microbiome regulatory interface during pouchitis. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0637-x) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s13059-015-0637-xen
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414286/pdf/en
dash.licenseLAAen_US
dc.titleAssociations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel diseaseen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalGenome Biologyen
dash.depositing.authorHuttenhower, Curtisen_US
dc.date.available2015-05-04T15:26:12Z
dc.identifier.doi10.1186/s13059-015-0637-x*
dash.authorsorderedfalse
dash.contributor.affiliatedHuttenhower, Curtis
dc.identifier.orcid0000-0002-1110-0096


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