The microbiota of cesarean-born infants can be partially restored to that of vaginally born infants immediately after birth. Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria—which were underrepresented in unexposed C-section–delivered infants—and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section–delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section–delivered babies.

Microaspiration is a common phenomenon in healthy subjects, but its frequency is increased in chronic inflammatory airway diseases, and its role in inflammatory and immune phenotypes is unclear. We have previously demonstrated that acellular bronchoalveolar lavage samples from half of the healthy people examined are enriched with oral taxa (here called pneumotype_SPT) and this finding is associated with increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage. Here, we have characterized the inflammatory phenotype using a multi-omic approach. By evaluating both upper airway and acellular bronchoalveolar lavage samples from 49 subjects from three cohorts without known pulmonary disease, we observed that pneumotype_SPT was associated with a distinct metabolic profile, enhanced expression of inflammatory cytokines, a pro-inflammatory phenotype characterized by elevated Th-17 lymphocytes and, conversely, a blunted alveolar macrophage TLR4 response. The cellular immune responses observed in the lower airways of humans with pneumotype_SPT indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.

The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that microaspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. To test this, we sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (nine never-smokers, 14 former-smokers, and six current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes, and neutrophils.

Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.