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

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.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0511-7) contains supplementary material, which is available to authorized users.

Influence of maternal microbiota during pregnancy on infant immunity

“…1). In addition, pups born to vancomycin breeders had significantly higher splenic cell counts, higher numbers of total B cells as well as follicular B cells versus control pups [1]. Indeed, we did not detect any vancomycin in maternal plasma 2 days after delivery, indicating that the antibiotic was not systemically absorbed.…”

“…Similarly, pups born to mothers treated with antibiotics orally during gestation and postpartum exhibited increased susceptibility to vaccinia virus infection and reduced interferon (IFN)-γ production by CD8 + T cells when compared to controls [21]. We recently showed, using mouse models, that altering maternal intestinal microbiota during pregnancy alone impacted inherent immunity in pups at 14 days postpartum [1] (Fig. We recently showed, using mouse models, that altering maternal intestinal microbiota during pregnancy alone impacted inherent immunity in pups at 14 days postpartum [1] (Fig.…”

“…We intended to only alter the microbiota in maternal gut and not at other body sites by administering oral vancomycin, which has poor oral bioavailability, during gestation. microbiota postpartum, suggesting that gut microbiota during pregnancy may also impact that at distal sites [1] and this may, in part, be a mechanism through which maternal gut microbiota influence neonatal immunity. Although the intervention was targeted to maternal gut in our model, we observed perturbations in breast milk microbiota, and to a lesser degree vaginal Fig.…”

“…Two lactic acid bacteria strains, Lactococcus lactis and L. salivarius, were orally administered to pregnant dams and later detected in mammary tissue and milk [27]. While the breast milk microbiota influences immune development postpartum [28][29][30], the composition of these microbiota is partly shaped prior to delivery and is dependent on gut microbiota during pregnancy [1]. Therefore, gut composition prior to delivery indirectly drives early offspring immune development via the gut-breast milk axis.…”

“…Vertical transmission of microbes from various maternal body sites contribute to the developing infant gut microbiota, including the gut, vagina, skin and breast milk [1,2]. The bacterial contingent of this community, the microbiota, are known to affect our health in profound ways, bringing to the forefront the symbiotic relationship that exists between these microbes and their human host.…”