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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.

The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13-deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning. During the learning process, wild-type mice increased the number of CD4 T cells in the meninges and production of IL-13, whereas neither Morris water maze-trained IL-4 nor trained IL-13-deficient mice were able to increase CD4 T cells in the meninges. Mechanistically, we showed that IL-13 is able to stimulate primary astrocytes to produce brain-derived neurotrophic factor, which does foster cognitive functions. Moreover, Morris water maze-trained wild-type mice were able to increase astrocyte-produced glial fibrillary acidic protein in the hippocampus, which was impaired in Morris water maze-trained IL-4- and IL-13-deficient mice. Collectively, this study strongly suggests that the Th2 cytokines, not only IL-4 but also IL-13, are involved in cognitive functions by stimulating astrocytes from the meninges and hippocampus. These results may be important for future development of therapeutic approaches associated with neurologic disorders such as Parkinson disease-associated dementia and HIV-associated dementia among others.