Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity
Donald D. Nyangahu,
Katie S. Lennard,
Bryan P. Brown,
Matthew G. Darby,
Jerome M. Wendoh,
Enock Havyarimana,
Peter Smith,
James Butcher,
Alain Stintzi,
Nicola Mulder,
William Horsnell,
Heather B. Jaspan
Affiliations
Donald D. Nyangahu
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
Katie S. Lennard
Institute of Infectious Diseases and Molecular Medicine, Department of Integrative Biomedical Sciences, Division of Computational Biology, University of Cape Town
Bryan P. Brown
Duke University
Matthew G. Darby
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
Jerome M. Wendoh
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
Enock Havyarimana
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
Peter Smith
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
James Butcher
Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa
Alain Stintzi
Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa
Nicola Mulder
Institute of Infectious Diseases and Molecular Medicine, Department of Integrative Biomedical Sciences, Division of Computational Biology, University of Cape Town
William Horsnell
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
Heather B. Jaspan
Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Division of Immunology, University of Cape Town
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.
