Delivery mode and perinatal antibiotics influence the predicted metabolic pathways of the gut microbiome.

Delivery mode and perinatal antibiotics influence gut microbiome composition in children. Most microbiome studies have used the sequencing of the bacterial 16S marker gene but have not reported the metabolic function of the gut microbiome, which may mediate biological effects on the host. Here, we used the PICRUSt2 bioinformatics tool to predict the functional profiles of the gut microbiome based on 16S sequencing in two child cohorts. Both Caesarean section and perinatal antibiotics markedly influenced the functional profiles of the gut microbiome at the age of 1 year. In machine learning analysis, bacterial fatty acid, phospholipid, and biotin biosynthesis were the most important pathways that differed according to delivery mode. Proteinogenic amino acid biosynthesis, carbohydrate degradation, pyrimidine deoxyribonucleotide and biotin biosynthesis were the most important pathways differing according to antibiotic exposure. Our study shows that both Caesarean section and perinatal antibiotics markedly influence the predicted metabolic profiles of the gut microbiome at the age of 1 year.

Microbiome of the first stool and overweight at age 3 years: A prospective cohort study.

BACKGROUND: Several reports have revealed that the first-pass meconium hosts a diverse microbiome, but its clinical significance is not known. OBJECTIVE: We designed a prospective population-based cohort study to evaluate whether the meconium microbiome predicts subsequent growth in children. METHODS: The study comprised 212 consecutive newborns with a meconium sample and a follow-up sample at 1 year of age. Trained nurses measured the children for weight and length using standardized techniques. We used next-generation sequencing of bacterial 16S rRNA gene and machine-learning approach for the analysis. RESULTS: The children with overweight at 3 years of age differed in their meconium microbiome from those with normal weight, having a higher proportion of Bacteroidetes phylum (29% vs 15%, P = .013). Using the machine-learning approach, the gut microbiome at birth predicted subsequent overweight with area under the curve 0.70 (SD 0.04). A lower proportion of Staphylococcus at birth was associated with greater length/height at 1 year (ß = -.68, P = .029) and 2 years of age (ß = -.74, P = .030). CONCLUSIONS: The microbiome of the first-pass meconium predicted subsequent overweight at the age of 3 years. The association between the gut microbiome and overweight appears to start already during pregnancy and at birth.

Microbiome of the first stool after birth and infantile colic.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 <0.001). CONCLUSIONS: 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.

Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.