Disrupted establishment of anaerobe and facultative anaerobe balance in preterm infants with extrauterine growth restriction.

Background: Extrauterine growth restriction (EUGR) in preterm birth infants could have long-term adverse impacts on health. Less is known about the gut microbiota regarding its establishment in early life and its role in long-term growth in preterm birth infants.

Methods: A prospective, longitudinal observational study was conducted with 67 preterm infants in a level III neonatal intensive care unit. Clinical information was obtained from medical records, and fecal samples were collected weekly during hospitalization and processed for 16S rRNA gene sequencing.

Results: The bacterial profiles from the weekly sampling of preterm infants demonstrated that the early-life gut microbiota was clustered into the following four stages in chronological order: stage 1: 0-4 days, stage 2: 1-2 weeks, stage 3: 3-7 weeks, and stage 4: 8-10 weeks. The development of gut microbiota showed latency at stage 4 in EUGR infants compared with that in non-EUGR infants, which resulted from their consistently high level of facultative anaerobes, including Enterobacteriaceae and , and lack of obligate anaerobes, including and . In the 2-year follow-up, infants with a high level of obligate anaerobes-to-facultative anaerobes ratio at stage 4 had a lower risk of long-term growth restriction at the margin of statistical significance.

Conclusion: The results of this study indicate that the development of gut microbiota in the early life of EUGR infants is delayed compared with that of non-EUGR infants. The obligate-to-facultative anaerobes ratio could be an indicator of the maturity of gut microbiota development and associated with the risk of long-term growth restriction in preterm infants.