Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery

Abstract

Human microbial communities are characterized by their taxonomic, metagenomic, and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to assess the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites, and assess the impact of mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early 3rd trimester (n=81) were prospectively enrolled for longitudinal sampling through 6 weeks post-delivery, and a second matched cross-sectional cohort (n=81) was additionally recruited for sampling once at delivery. Samples were collected for each maternal-infant dyad across multiple body sites, including stool, oral gingiva, nares, skin and vagina. 16S rRNA gene sequencing analysis and whole genome shotgun sequencing was performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogenous across all body sites at delivery, with the notable exception of neonatal meconium. However, by 6 weeks, the infant microbiota structure and function had significantly expanded and diversified, with body site serving as the primary determinant of the bacterial community composition and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with Cesarean delivery in some body sites (oral, nares, and skin; R2 = 0.038), this was not true in neonatal stool (meconium, Mann-Whitney p>0.05) and there was no observable difference in community function regardless of delivery mode. By 6 weeks of age, the infant microbiota structure and function had expanded and diversified with demonstrable body site specificity (p<0.001, R2 = 0.189), and no discernable differences in neither community structure nor function by Cesarean delivery were identifiable (p=0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes significant reorganization that is primarily driven by body site and not by mode of delivery.

Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose?

“…In agreement with earlier studies, we observed that microbiota residing in different body sites were highly differentiated (Chu et al, 2017;Huttenhower et al, 2012). This differentiation was already clear in 3 day old infants and very pronounced in 3 week old infants.…”

“…The differences between vaginally delivered and Caesareansection delivered infants are apparent in early days and weeks and diminish with time (Dogra et al, 2015;Stokholm et al, 2016), which may explain the relatively minor effects reported in some studies (Chu et al, 2017). Vaginally delivered, breastfed infants had microbiota dominated by bifidobacteria.…”

“…Yet, transient passage, however consequential, should not be confused with seeding infant gut colonisation. Chu and colleagues (Chu et al, 2017) in a recent study of stool microbiota in 52 infants from the USA, found little difference in similarity to maternal vaginal OTUs between the infant stool microbiome sampled at six weeks relative to delivery mode. In a proof of concept study of 7 infants, Dominguez-Bello et al (2016) showed that exposure of Caesarean section delivered infants to maternal vaginal microbiota resulted in infant skin microbiota that resembled that of vaginally delivered infants.…”

Cleaning up the hygiene hypothesis

“…But the study was small-only four C-section babies were swabbed-and the long-term effect on their immune regulation remains unknown. What's more, a recent study of 162 mother-infant pairs suggests that C-sections have no discernible effect on the infant microbiome by 6 weeks of age (19).…”

Intestinal Microbiota: Early Formation, Health Effects, and Correction Ways

“…Применение анти-биотикотерапии при родах или в постнатальном периоде, особенно необоснованное, ведет к уменьшению в кишеч-ной микробиоте младенца количества Bacteroides и уве-личению представителей класса Clostridia [30]. Небла-го приятно сказывается антибиотикотерапия кормящих матерей в послеродовом периоде и на микробиоте груд-ного молока: уменьшается количество бифидо-и лакто-бактерий в грудном молоке, а в кишечной микробиоте ребенка, соответственно, увеличивается относительное содержание Clostridium difficile и Enterococcus [31,32].…”