Multiomic Analyses of Nascent Preterm Infant Microbiomes Differentiation Suggest Opportunities for Targeted Intervention

The first week after birth is a critical time for the establishment of microbial communities for infants. Preterm infants face unique environmental impacts on their newly acquired microbiomes, including increased incidence of cesarean section delivery and exposure to antibiotics as well as delayed enteral feeding and reduced human interaction during their intensive care unit stay. Using contextualized paired metabolomics and 16S sequencing data, the development of the gut, skin, and oral microbiomes of infants is profiled daily for the first week after birth, and it is found that the skin microbiome appears robust to early life perturbation, while direct exposure of infants to antibiotics, rather than presumed maternal transmission, delays microbiome development and prevents the early differentiation based on body site regardless of delivery mode. Metabolomic analyses identify the development of all gut metabolomes of preterm infants toward full‐term infant profiles, but a significant increase of primary bile acid metabolism only in the non‐antibiotic treated vaginally birthed late preterm infants. This study provides a framework for future multi‐omic, multibody site analyses on these high‐risk preterm infant populations and suggests opportunities for monitoring and intervention, with infant antibiotic exposure as the primary driver of delays in microbiome development. Daily, multibody‐site microbiome sampling for the first week of life reveals that preterm infant antibiotic exposure delays the differentiation of body‐site specific microbiomes. Primary bile acid metabolism in the gut metabolome is also present only in the non‐antibiotic‐treated, vaginally birthed preterm infants, further highlighting the disruptive impact of antibiotics. This study provides a framework for future studies of infant microbiome development.