Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs

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dc.contributor.authorTwitchell, Ericaen
dc.contributor.authorTin, Christineen
dc.contributor.authorWen, Keen
dc.contributor.authorZhang, Husenen
dc.contributor.authorBecker-Dreps, Sylviaen
dc.contributor.authorAzcarate-Peril, M. Andreaen
dc.contributor.authorVilchez, Samuelen
dc.contributor.authorLi, Guohuaen
dc.contributor.authorRamesh, Ashwinen
dc.contributor.authorWeiss, Mariahen
dc.contributor.authorLei, Shaohuaen
dc.contributor.authorBui, Tammyen
dc.contributor.authorYang, Xingdongen
dc.contributor.authorSchultz-Cherry, Stacey L.en
dc.contributor.authorYuan, Lijuanen
dc.date.accessioned2017-02-22T15:41:05Zen
dc.date.available2017-02-22T15:41:05Zen
dc.date.issued2016en
dc.description.abstractBACKGROUND: Rotavirus vaccines have poor efficacy in infants from low- and middle-income countries. Gut microbiota is thought to influence the immune response to oral vaccines. Thus, we developed a gnotobiotic (Gn) pig model of enteric dysbiosis to study the effects of human gut microbiota (HGM) on immune responses to rotavirus vaccination, and the effects of rotavirus challenge on the HGM by colonizing Gn pigs with healthy HGM (HHGM) or unhealthy HGM (UHGM). The UHGM was from a Nicaraguan infant with a high enteropathy score (ES) and no seroconversion following administration of oral rotavirus vaccine, while the converse was characteristic of the HHGM. Pigs were vaccinated, a subset was challenged, and immune responses and gut microbiota were evaluated. RESULTS: Significantly more rotavirus-specific IFN-γ producing T cells were in the ileum, spleen, and blood of HHGM than those in UHGM pigs after three vaccine doses, suggesting HHGM induces stronger cell-mediated immunity than UHGM. There were significant correlations between multiple Operational Taxonomic Units (OTUs) and frequencies of IFN-γ producing T cells at the time of challenge. There were significant positive correlations between Collinsella and CD8+ T cells in blood and ileum, as well as CD4+ T cells in blood, whereas significant negative correlations between Clostridium and Anaerococcus, and ileal CD8+ and CD4+ T cells. Differences in alpha diversity and relative abundances of OTUs were detected between the groups both before and after rotavirus challenge. CONCLUSION: Alterations in microbiome diversity and composition along with correlations between certain microbial taxa and T cell responses warrant further investigation into the role of the gut microbiota and certain microbial species on enteric immunity. Our results support the use of HGM transplanted Gn pigs as a model of human dysbiosis during enteric infection, and oral vaccine responses.en
dc.description.versionPublished versionen
dc.format.extent51 - ? page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1186/s13099-016-0136-yen
dc.identifier.urihttp://hdl.handle.net/10919/75128en
dc.identifier.volume8en
dc.language.isoenen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27826359en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectEnteric dysbiosisen
dc.subjectEnteric immunityen
dc.subjectGnotobiotic pigen
dc.subjectRotavirusen
dc.subjectVaccineen
dc.titleModeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigsen
dc.title.serialGut Pathogensen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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