Plain language summary
The gut microbiota is key for immune development, especially during a critical window in infancy, and it has been shown that maternal diet before, during and after pregnancy influences infant metabolism and gut microbiota. The aim of this study was to assess the effects of maternal antibiotics administration during gestation and nursing on offspring gut microbiota and immunity. Pregnant mice, dams, received oral vancomycin in drinking water 5 days prior to give birth (gestation group), 14 days after delivery (nursing group) or 5 days prior to delivery and throughout nursing (gestation plus nursing group), while control mice received no vancomycin. Adaptive immunity and gut microbiota in dams and pups were analysed at various times after delivery. This study showed that antibiotic alteration of maternal gut microbiota during both pregnancy and nursing results in changes in the adaptive immunity in offspring. The authors conclude these findings are important as they provide insight into the mechanism by which maternal exposures during pregnancy may impact infant health, therefore identifying potential targets for intervention.
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.
Methodological quality
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