Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs
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Twitchell, Erica L, et al. Modeling Human Enteric Dysbiosis and Rotavirus Immunity In Gnotobiotic Pigs. BioMed Central, 2016. https://doi.org/10.17615/vb9f-f946APA
Twitchell, E., Tin, C., Wen, K., Zhang, H., Becker Dreps, S., Azcarate Peril, A., Vilchez, S., Li, G., Ramesh, A., Weiss, M., Lei, S., Bui, T., Yang, X., Schultz Cherry, S., & Yuan, L. (2016). Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs. BioMed Central. https://doi.org/10.17615/vb9f-f946Chicago
Twitchell, Erica L, Christine Tin, Ke Wen, Husen Zhang, Sylvia Becker Dreps, Andrea Azcarate Peril, Samuel Vilchez et al. 2016. Modeling Human Enteric Dysbiosis and Rotavirus Immunity In Gnotobiotic Pigs. BioMed Central. https://doi.org/10.17615/vb9f-f946- Creator
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Twitchell, Erica L
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Tin, Christine
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Wen, Ke
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Zhang, Husen
- Other Affiliation: Microbiome Core, Cancer Inflammation Program, National Cancer Institute, Bethesda, USA
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Becker-Dreps, Sylvia
- Affiliation: School of Medicine, Department of Family Medicine
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Azcarate-Peril, Andrea
- Affiliation: Center for Gastrointestinal Biology and Disease
- Other Affiliation: Microbiome Core Facility
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Vilchez, Samuel
- Other Affiliation: Department of Microbiology and Parasitology, Faculty of Medical Sciences, National Autonomous University of Nicaragua, León, Nicaragua
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Li, Guohua
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Ramesh, Ashwin
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Weiss, Mariah
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Lei, Shaohua
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Bui, Tammy
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Yang, Xingdong
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
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Schultz-Cherry, Stacey
- Other Affiliation: Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, USA
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Yuan, Lijuan
- Other Affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, USA
- Abstract
- Background 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.
- Date of publication
- November 8, 2016
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- The Author(s)
- Journal title
- Gut Pathogens
- Journal volume
- 8
- Journal issue
- 1
- Page start
- 51
- Language
- English
- Bibliographic citation
- Gut Pathogens. 2016 Nov 08;8(1):51
- Publisher
- BioMed Central
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