Abstract
BackgroundEarly 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.ResultsIn 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.ConclusionOur results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.
Highlights
Life microbiota is an important determinant of immune and metabolic development and may have lasting consequences
Maternal gut microbiota during gestation and nursing differentially shape infant mouse intestinal microbiota To assess the impact of maternal gut microbiota during fetal development and nursing on infant microbiota, we treated pregnant dams with oral vancomycin for 5 days prior to delivery, for 14 days postpartum during nursing, or both and compared these to control dams (Mc) (Fig. 1a)
We observed significantly reduced α-diversity, in pups born to dams treated with vancomycin during nursing (Pn) or gestation plus nursing (Pgn) compared to pups born to control dams (Pc) (Fig. 1b)
Summary
Life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. The fetal gut has long been assumed to be sterile, with colonization occurring only at delivery [2] Controversial, this dogma has recently been challenged with the apparent identification of low abundance bacteria in fetal membranes, Antibiotics, necessary in some cases, can lead to disruption of the commensal bacteria with lasting consequences [15, 16]. Using oral vancomycin, which has low oral bioavailability, we show that alteration of maternal gut microbiome during gestation, nursing, or both has persistent effects on offspring gut microbiota and systemic adaptive immunity
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