The intestinal microbiome is a unique ecosystem that influences metabolism in humans. Experimental evidence indicates that intestinal microbiota can transfer an obese phenotype from humans to mice. Since mothers transmit intestinal microbiota to their offspring during labor, we hypothesized that among vaginal deliveries, maternal body mass index is associated with neonatal gut microbiota composition. We report the association of maternal pre-pregnancy body mass index on stool microbiota from 74 neonates, 18 born vaginally (5 to overweight or obese mothers) and 56 by elective C-section (26 to overweight or obese mothers). Compared to neonates delivered vaginally to normal weight mothers, neonates born to overweight or obese mothers had a distinct gut microbiota community structure (weighted UniFrac distance PERMANOVA, p < 0.001), enriched in Bacteroides and depleted in Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus. We show that these microbial signatures are predicted to result in functional differences in metabolic signaling and energy regulation. In contrast, among elective Cesarean deliveries, maternal body mass index was not associated with neonatal gut microbiota community structure (weighted UniFrac distance PERMANOVA, p = 0.628). Our findings indicate that excess maternal pre-pregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, but not Cesarean delivery. These differences may translate to altered maintenance of metabolic health in the offspring.
Cesarean (C-section) delivery, recently shown to cause excess weight gain in mice, perturbs human neonatal gut microbiota development due to the lack of natural mother-to-newborn transfer of microbes. Neonates excrete first the in-utero intestinal content (referred to as meconium) hours after birth, followed by intestinal contents reflective of extra-uterine exposure (referred to as transition stool) 2 to 3 days after birth. It is not clear when the effect of C-section on the neonatal gut microbiota emerges. We examined bacterial DNA in carefully-collected meconium, and the subsequent transitional stool, from 59 neonates [13 born by scheduled C-section and 46 born by vaginal delivery] in a private hospital in Brazil. Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced using the Illumina MiSeq (San Diego, CA, USA) platform. We found evidence of bacterial DNA in the majority of meconium samples in our study. The bacterial DNA structure (i.e., beta diversity) of meconium differed significantly from that of the transitional stool microbiota. There was a significant reduction in bacterial alpha diversity (e.g., number of observed bacterial species) and change in bacterial composition (e.g., reduced Proteobacteria) in the transition from meconium to stool. However, changes in predicted microbiota metabolic function from meconium to transitional stool were only observed in vaginally-delivered neonates. Within sample comparisons showed that delivery mode was significantly associated with bacterial structure, composition and predicted microbiota metabolic function in transitional-stool samples, but not in meconium samples. Specifically, compared to vaginally delivered neonates, the transitional stool of C-section delivered neonates had lower proportions of the genera Bacteroides, Parabacteroides and Clostridium. These differences led to C-section neonates having lower predicted abundance of microbial genes related to metabolism of amino and nucleotide sugars, and higher abundance of genes related to fatty-acid metabolism, amino-acid degradation and xenobiotics biodegradation. In summary, microbiota diversity was reduced in the transition from meconium to stool, and the association of delivery mode with microbiota structure, composition and predicted metabolic function was not observed until the passing of the transitional stool after meconium.
The associations of Cesarean delivery with offspring metabolic and immune-mediated diseases are believed to derive from lack of mother-to-newborn transmission of specific microbes at birth. Bifidobacterium spp., in particular, has been hypothesized to play a health-promoting role, yet little is known about how delivery mode modifies colonization of the newborn by this group of microbes. The aim of this research was to examine the presence of Bifidobacterium in meconium and in the transitional stool, and to assess cytokine levels and hematological parameters in the venous cord blood of infants born by elective, pre-labor Cesarean section vs. vaginal delivery in Southern Brazil. We recruited 89 mother-newborn pairs (23 vaginal delivery and 66 elective cesarean delivery), obtained demographic information from a structured questionnaire and clinical information from medical records. We obtained umbilical cord venous blood and meconium samples following delivery and the transitional stool (the first defecation after meconium) before discharge. We determined plasma levels of IL-1β, IL-10, IL-6, GM-CSF, IL-5, IFN-γ, TNF-α, IL-2, IL-4 and IL-8 in the cord blood, and presence of stool Bifidobacterium by real time PCR. Compared to vaginally-delivered neonates, Cesarean-delivered neonates had a lower leukocyte count (p = 0.037), lower hemoglobin (p = 0.04), and lower levels of the cytokine GM-CSF (p = 0.009) in the cord blood. Moreover, Bifidobacterium was detected less often in the transitional stool of Cesarean-delivered neonates compared to vaginally-delivered neonates (p = 0.001). The results indicate that pre-labor Cesarean birth may be associated with microbial and hematological alterations in the neonate. The clinical significance of these findings remains to be determined in larger prospective birth cohort studies.
BackgroundC‐section (CS) babies have elevated risk of obesity, perhaps due to differences in gut microbiota during critical windows of metabolic programming. While known that the newborn gut microbiota differ by delivery mode, it is unclear when these differences emerge.AimsHere we examine how delivery mode is associated with microbiota in neonate 1st (meconium) and 2nd stool.MethodsOur study comprises 62 neonates born by elective CS and 21 by vaginal delivery (VD) from Porto Alegre, Brazil. Bacterial V4 16SrRNA region was sequenced with the Illumina platform. Analyses were performed using QIIME. Linear discriminant analysis (LDA) effect size (LEfSe) method, which integrates statistical significance and biologic relevance, was used to compare the gut microbiota between CS and VD babies.ResultsIn the meconium, there were no differences in microbial diversity or community structure between CS and VD babies. However, in the 2nd stool, compared to CS babies, VD neonates had greater relative abundance of 4 phylotypes, including Bacteroides genus, and lower relative abundance of 19 phylotypes.imageCompared to VD babies, the 2nd stool from CS babies also appeared to have more microbial diversity, but this difference was not statistically significant (p=0.33). Findings were similar across pregnancy weight strata.ConclusionsCS babies have disrupted gut microbiota compared to VD babies, but, in our study, these differences do not emerge until the 2nd stool. Further research is needed to elucidate what determines the microbial composition of meconium, and whether the differences in 2nd stool microbiota by delivery mode have long‐term health consequences.
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