Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity

dc.contributor.authorNyangahu, Donald D
dc.contributor.authorLennard, Katie S
dc.contributor.authorBrown, Bryan P
dc.contributor.authorDarby, Matthew G
dc.contributor.authorWendoh, Jerome M
dc.contributor.authorHavyarimana, Enock
dc.contributor.authorSmith, Peter
dc.contributor.authorButcher, James
dc.contributor.authorStintzi, Alain
dc.contributor.authorMulder, Nicola
dc.contributor.authorHorsnell, William
dc.contributor.authorJaspan, Heather B
dc.date.accessioned2018-07-12T06:59:40Z
dc.date.available2018-07-12T06:59:40Z
dc.date.issued2018-07-07
dc.date.updated2018-07-08T03:42:31Z
dc.description.abstractBackground: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery. Results In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells. Conclusion Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.
dc.identifier.apacitationNyangahu, D. D., Lennard, K. S., Brown, B. P., Darby, M. G., Wendoh, J. M., Havyarimana, E., ... Jaspan, H. B. (2018). Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity. <i>Microbiome</i>, http://hdl.handle.net/11427/28299en_ZA
dc.identifier.chicagocitationNyangahu, Donald D, Katie S Lennard, Bryan P Brown, Matthew G Darby, Jerome M Wendoh, Enock Havyarimana, Peter Smith, et al "Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity." <i>Microbiome</i> (2018) http://hdl.handle.net/11427/28299en_ZA
dc.identifier.citationNyangahu, D. D., Lennard, K. S., Brown, B. P., Darby, M. G., Wendoh, J. M., Havyarimana, E., ... & Horsnell, W. (2018). Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity. Microbiome, 6(1), 124.
dc.identifier.ris TY - Journal Article AU - Nyangahu, Donald D AU - Lennard, Katie S AU - Brown, Bryan P AU - Darby, Matthew G AU - Wendoh, Jerome M AU - Havyarimana, Enock AU - Smith, Peter AU - Butcher, James AU - Stintzi, Alain AU - Mulder, Nicola AU - Horsnell, William AU - Jaspan, Heather B AB - Background: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery. Results In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells. Conclusion Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity. DA - 2018-07-07 DB - OpenUCT DP - University of Cape Town J1 - Microbiome LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity TI - Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity UR - http://hdl.handle.net/11427/28299 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s40168-018-0511-7
dc.identifier.urihttp://hdl.handle.net/11427/28299
dc.identifier.vancouvercitationNyangahu DD, Lennard KS, Brown BP, Darby MG, Wendoh JM, Havyarimana E, et al. Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity. Microbiome. 2018; http://hdl.handle.net/11427/28299.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceMicrobiome
dc.source.urihttps://microbiomejournal.biomedcentral.com/
dc.titleDisruption of maternal gut microbiota during gestation alters offspring microbiota and immunity
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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