Kyung E. Rhee

Abstract A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia 1 . The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition, but we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes 2 . A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host lipids; such as sphingolipids and bile acids 3–11 . These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. Considering the diversity of the human microbiome, numbering over 40,000 operational taxonomic units 12 , a plethora of molecular diversity remains to be discovered. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model 13–15 to provide an untargeted assessment of the chemical diversity between germ-free (GF) and colonized mice (specific-pathogen free, SPF), and report the finding of novel bile acids produced by the microbiome in both mice and humans that have evaded characterization despite 170 years of research on bile acid chemistry 16 .

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.