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Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity
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 preg...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035804/ https://www.ncbi.nlm.nih.gov/pubmed/29981583 http://dx.doi.org/10.1186/s40168-018-0511-7 |
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author | Nyangahu, Donald D. Lennard, Katie S. Brown, Bryan P. Darby, Matthew G. Wendoh, Jerome M. Havyarimana, Enock Smith, Peter Butcher, James Stintzi, Alain Mulder, Nicola Horsnell, William Jaspan, Heather B. |
author_facet | Nyangahu, Donald D. Lennard, Katie S. Brown, Bryan P. Darby, Matthew G. Wendoh, Jerome M. Havyarimana, Enock Smith, Peter Butcher, James Stintzi, Alain Mulder, Nicola Horsnell, William Jaspan, Heather B. |
author_sort | Nyangahu, Donald D. |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0511-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6035804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60358042018-07-12 Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity Nyangahu, Donald D. Lennard, Katie S. Brown, Bryan P. Darby, Matthew G. Wendoh, Jerome M. Havyarimana, Enock Smith, Peter Butcher, James Stintzi, Alain Mulder, Nicola Horsnell, William Jaspan, Heather B. Microbiome Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-018-0511-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-07 /pmc/articles/PMC6035804/ /pubmed/29981583 http://dx.doi.org/10.1186/s40168-018-0511-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Nyangahu, Donald D. Lennard, Katie S. Brown, Bryan P. Darby, Matthew G. Wendoh, Jerome M. Havyarimana, Enock Smith, Peter Butcher, James Stintzi, Alain Mulder, Nicola Horsnell, William Jaspan, Heather B. Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
title | Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
title_full | Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
title_fullStr | Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
title_full_unstemmed | Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
title_short | Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
title_sort | disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035804/ https://www.ncbi.nlm.nih.gov/pubmed/29981583 http://dx.doi.org/10.1186/s40168-018-0511-7 |
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