Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity

dc.contributor.advisorJaspan, Heather Ben_ZA
dc.contributor.advisorHorsnell, Williamen_ZA
dc.contributor.authorNyangahu, Donald Den_ZA
dc.date.accessioned2017-10-02T13:05:06Z
dc.date.available2017-10-02T13:05:06Z
dc.date.issued2017en_ZA
dc.description.abstractMaternal microbiota during pregnancy, as well as maternal disease state, may impact offspring gut bacterial colonisation. Here, we explore the impact of maternal antibiotics during gestation and/or nursing on offspring gut microbiota. Further, we investigate the effect of preconception helminth infections on maternal and infant gut microbiota. For maternal antibiotic experiments, dams were fed vancomycin, polymyxin B, or both, in drinking water during gestation, nursing or gestation plus nursing, and their offspring microbiota analysed at 14 days of life, alongside immunity in the spleens. Offspring born to vancomycin treated mothers had significantly higher relative abundance of Proteobacteria and Tenericutes while maternal oral polymyxin B led to significantly lower abundance of Proteobacteria and Deferribacteres in infants. Maternal oral vancomycin led to significant reduction in proportions of infant central memory CD4+ T cells (CD4+CD44hiCD62Lhi) regardless of antibiotic timing. Effector memory CD4+ T cells were significantly lower in pups born to dams treated with polymyxin B while nursing while proportions of central memory CD4 T cells were significantly increased in gestation only or gestation plus nursing pups. In addition, oral vancomycin in dams during nursing resulted in significantly reduced proportions of both total and follicular B cells in offspring born to antibiotic treated dams. Pups born to Vancomycin treated mothers had a significant delay in growth when infected with Respiratory Syncytial Virus (RSV). On the other hand, pups born to mothers treated with Polymyxin B during gestation or gestation plus nursing were susceptible to Nippostrongylus brasiliensis (Nb) infection. In the second study, we infected female BALB/c mice with 500Nb L3 three weeks prior to mating and examined the effect of preconception helminth infection on offspring microbiota and immunity. Preconception Nb infections led to alterations of maternal gut microbiota during pregnancy. In addition, we observed dramatic differences in offspring microbiota in pups born to previously helminth infected dams. Coriobacteriaceae were predominant in pups born to previously Nb infected dams when compared to uninfected dams. Overall, manipulation of maternal microbiota during gestation or lactation profoundly impacts offspring growth, intestinal microbiota and immunity to RSV and helminths.en_ZA
dc.identifier.apacitationNyangahu, D. D. (2017). <i>Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Immunology. Retrieved from http://hdl.handle.net/11427/25479en_ZA
dc.identifier.chicagocitationNyangahu, Donald D. <i>"Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Immunology, 2017. http://hdl.handle.net/11427/25479en_ZA
dc.identifier.citationNyangahu, D. 2017. Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Nyangahu, Donald D AB - Maternal microbiota during pregnancy, as well as maternal disease state, may impact offspring gut bacterial colonisation. Here, we explore the impact of maternal antibiotics during gestation and/or nursing on offspring gut microbiota. Further, we investigate the effect of preconception helminth infections on maternal and infant gut microbiota. For maternal antibiotic experiments, dams were fed vancomycin, polymyxin B, or both, in drinking water during gestation, nursing or gestation plus nursing, and their offspring microbiota analysed at 14 days of life, alongside immunity in the spleens. Offspring born to vancomycin treated mothers had significantly higher relative abundance of Proteobacteria and Tenericutes while maternal oral polymyxin B led to significantly lower abundance of Proteobacteria and Deferribacteres in infants. Maternal oral vancomycin led to significant reduction in proportions of infant central memory CD4+ T cells (CD4+CD44hiCD62Lhi) regardless of antibiotic timing. Effector memory CD4+ T cells were significantly lower in pups born to dams treated with polymyxin B while nursing while proportions of central memory CD4 T cells were significantly increased in gestation only or gestation plus nursing pups. In addition, oral vancomycin in dams during nursing resulted in significantly reduced proportions of both total and follicular B cells in offspring born to antibiotic treated dams. Pups born to Vancomycin treated mothers had a significant delay in growth when infected with Respiratory Syncytial Virus (RSV). On the other hand, pups born to mothers treated with Polymyxin B during gestation or gestation plus nursing were susceptible to Nippostrongylus brasiliensis (Nb) infection. In the second study, we infected female BALB/c mice with 500Nb L3 three weeks prior to mating and examined the effect of preconception helminth infection on offspring microbiota and immunity. Preconception Nb infections led to alterations of maternal gut microbiota during pregnancy. In addition, we observed dramatic differences in offspring microbiota in pups born to previously helminth infected dams. Coriobacteriaceae were predominant in pups born to previously Nb infected dams when compared to uninfected dams. Overall, manipulation of maternal microbiota during gestation or lactation profoundly impacts offspring growth, intestinal microbiota and immunity to RSV and helminths. DA - 2017 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity TI - Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity UR - http://hdl.handle.net/11427/25479 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/25479
dc.identifier.vancouvercitationNyangahu DD. Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Immunology, 2017 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/25479en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherClinical Science and Immunologyen_ZA
dc.titleAlterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunityen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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