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

Publication

https://doi.org/10.1186/s40168-018-0511-7

Domain

Fellow

Nyangahu et al. Microbiome (2018) 6:124

Donald D. Nyangahu^1,8, Katie S. Lennard², Bryan P. Brown^3,8, Matthew G. Darby¹, Jerome M. Wendoh¹,
Enock Havyarimana¹, Peter Smith¹, James Butcher⁴, Alain Stintzi⁴, Nicola Mulder², William Horsnell^1,5,6†
and Heather B. Jaspan^1,7*†

* Correspondence: hbjaspan@gmail.com

^†William Horsnell and Heather B. Jaspan contributed equally to this work.
¹Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town, Cape Town, South Africa.

²Institute of Infectious Diseases and Molecular Medicine, Department of Integrative Biomedical Sciences, Division of Computational Biology, University of Cape Town, Cape Town, South Africa.

³Duke University, Durham, NC, USA.

⁴Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, CA, USA.

⁵Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK.

⁶Laboratory of Molecular and Experimental Immunology and Neurogenetics, UMR 7355, CNRS-University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, 45000 Orléans, France.

⁷Department of Pediatrics and Global Health, University of Washington and Center for Global Infectious Disease
Research, Seattle Children’s Research Institute, Seattle, WA, USA.

⁸Present Address: Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, WA, USA.

Abstract

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.

Keywords

Microbiota Influence

Offspring Immunity

Stomach Contents

Breast Milk

Early-life Microbiota

Published by

Microbiome