The microbiome and metabolome of pre-term infant stool is personalized, and not driven by health outcomes including necrotizing enterocolitis and late-onset sepsis

Abstract The assembly and development of the gut microbiome in infants has important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birthweight preterm infants over the first six weeks of life. Infant health outcomes included healthy, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized the bacterial composition by 16S rRNA gene sequencing and metabolome by untargeted gas chromatography mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus due to the near uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to which baby the sample came from (Permanova R2=0.48, p<0.001), while clinical status (healthy, NEC, or late-onset sepsis), and overlapping time in the NICU did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (Permanova R2=0.43, p<0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05 (p = 0.03 ± 0.03). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis or a healthy outcome. Overall, preterm infants gut microbial communities were personalized and reflected antibiotic usage. ImportancePreterm infants face health problems likely related to microbial exposures including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from thirty-two preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found the preterm infant microbiome and metabolome were both personalized, and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangling the health consequences of the preterm infant microbiome.