Postnatal age is strongly correlated with the early development of the gut microbiome in preterm infants

BACKGROUND: The gut microbiome plays a potential role in clinical events in preterm infants and may affect their lateral development. Understanding the initial colonization of microbes in the gut, their early dynamic changes, and the major factors correlated with these changes would provide crucial information about the developmental process in early life. METHODS: The present study enrolled 151 preterm infants and examined the longitudinal dynamics of their fecal microbiome profiles during the period of hospitalization using 16S ribosomal RNA gene sequencing. Random forest modeling was used to predict postnatal age (Age), postmenstrual age (PMA), and gestational age (GA), using gut microbiome features. RESULTS: Principal coordinate analysis revealed that the gut microbiome of the preterm infants displayed an obvious time-dependent change pattern, which showed the strongest association with Age, followed by PMA, and a much weaker association with (GA). Random forest modeling further evidenced the time-dependent change pattern, with the Pearson’s correlation coefficients between the actual values and the gut microbiome-predicted values being 0.68, 0.53, and 0.38 for postnatal, postmenstrual, and gestational age, respectively. The microbiome dynamism could be further divided into four Age stages, each with its own characteristic microbial taxa. The first 1–4 days (T1 stage) represented the meconium microbiome, with colonization of a high diversity of microbes before or during delivery. During 5–15 days (T2 stage), the gut microbiome of the preterm infants underwent a rapid turnover, in which microbial diversity declined, and stabilized afterward. Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Staphylococcaceae, and Clostridiaceae were the major classes in the gut microbiome in the lateral stages of development (T3–T4 stage). CONCLUSIONS: Postnatal age, rather than the gestational age, is significantly correlated with the gut microbiome of preterm infants, suggesting that clinical interventions contribute more to the early dynamics of gut microbiome in preterm infants than the natural development of the gut.