Fetal exposures and perinatal influences on the stool microbiota of premature infants

Abstract

Objective: To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants.

Methods: Forty-nine serial stool samples were obtained weekly from nine extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development.

Results: Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family Enterobacteriaceae.

Conclusions: We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time.

• Antibiotics
• chorioamnionitis
• microbiome
• obstetrical complications
• obstetrical interventions
• PPPROM
• prematurity

Acknowledgements

The authors are deeply grateful to the children and families that made this study possible. We would also like to acknowledge the efforts of the nurses and staff in the Dartmouth-Hitchcock intensive care nursery. Special thanks to Dr. Olga Zhaxybayeva for helpful discussions. We also thank Dr. Tom Caldwell for database creation and management.

Declaration of interest

The authors report no declaration of interest.

JCM is a member of the Children's Environmental Health and Disease Prevention Research Center at Dartmouth (P01ES022832 from NIEHS and RD83544201 from the EPA) as well as the Molecular Epidemiology Center at Dartmouth COBRE (NIGMS P20 GM104416). JCM also received funds from the Hearst Foundation, the Joshua Burnett Career Development Award through the Hitchcock Foundation (Dartmouth), the CF Foundation Harry Shwachman Clinical Investigator Award. DCK was supported by a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research # KL2TR000119. Additionally, this work was supported by: the Neukom Institute (JHM); NIH grants K01LM011985 (AGH); R01AI59694, GM103534, GM103506 (JHM); 5T32DK007301-35 (DAC); 4UH3DK 083993 (MLS and HGM); K24AT003683 (PLH).

Supplementary material available online

Supplementary figures and tables.