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Background Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods. Methods We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics. Results We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant. Conclusions Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods. Impact We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants. This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods. This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.

Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

Recent studies have shown a diverse microbiome in the first stool after birth. The clinical significance of the microbiome of the first stool is not known. Infantile colic has earlier been associated with the composition of the intestinal microbiome. We set out to test whether the microbiome of the first stool is associated with subsequent infantile colic in a prospective, population-based cohort study of 212 consecutive newborn infants. We used next-generation sequencing of the bacterial 16S rRNA gene. The newborns who later developed infantile colic (n = 19) had a lower relative abundance of the genus Lactobacillus and the phylum Firmicutes in the first stool than those who remained healthy (n = 139). By using all microbiome data, random forest algorithm classified newborn with subsequent colic and those who remained healthy with area under the curve of 0.66 (SD 0.03) as compared to that of shuffled samples (P value

Meconium is formed before birth and may reflect the microbiome of the fetus. To test our hypothesis, we investigated whether maternal factors during pregnancy, such as biodiversity of the living environment, influence the microbiome of the first stool more than immediate perinatal factors. We recruited 218 consecutive newborn infants from one hospital. Regions of the bacterial 16S rRNA gene were sequenced to characterize the microbiomes of the first-pass meconium samples (N=212). We used a multivariate model to determine both the prenatal and perinatal factors affecting the microbiome. The number of operational taxonomic units ranged from 0 to 448 per newborn. The most abundant phyla were Firmicutes, with a relative abundance of 44%, Proteobacteria, 28%, and Bacteroidetes, 15%. By a multivariate analysis, the biodiversity of the home environment increased the diversity of microbiomes, whereas perinatal factors, such as the delivery mode or exposure to antimicrobials during labor did not have an effect. The microbiome of the first-pass meconium was not altered by immediate perinatal factors, but was affected by maternal factors during pregnancy, implying the in utero transfer of microbes and the development of the gut microbiota niche in fetal life.

Recent studies have shown a diverse microbiome in the first stool after birth. The clinical significance of the microbiome of the first stool is not known. Infantile colic has earlier been associated with the composition of the intestinal microbiome.We set out to test whether the microbiome of the first stool is associated with subsequent infantile colic in a prospective, population-based cohort study of 212 consecutive newborn infants. We used next-generation sequencing of the bacterial 16S rRNA gene.The newborns who later developed infantile colic (n = 19) had a lower relative abundance of the genus Lactobacillus and the phylum Firmicutes in the first stool than those who remained healthy (n = 139). By using all microbiome data, random forest algorithm classified newborn with subsequent colic and those who remained healthy with area under the curve of 0.66 (SD 0.03) as compared to that of shuffled samples (P value0.001).In this prospective, population-based study, the microbiome of the first-pass meconium was associated with subsequent infantile colic. Our results suggest that the pathogenesis of infantile colic is closely related to the intestinal microbiome at birth.