Fetal exposures and perinatal influences on the stool microbiota of premature infants.
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.
a Department of Genetics , Institute for Quantitative Biomedical Sciences, Geisel School of Medicine, Dartmouth College , Hanover , NH , USA .
Diana A
DA
Chernikova
b Department of Biostatistics , University of Kansas Medical Center , Kansas City , KS , USA .
Devin C
DC
Koestler
c Department of Epidemiology , Geisel School of Medicine, Dartmouth College , Hanover , NH , USA .
Anne Gatewood
AG
Hoen
d Department of Microbiology and Immunology , Geisel School of Medicine, Dartmouth College , Hanover , NH , USA .
Molly L
ML
Housman
e Division of Global Health, Department of Pediatrics , Massachusetts General Hospital , Boston , MA , USA .
Patricia L
PL
Hibberd
a Department of Genetics , Institute for Quantitative Biomedical Sciences, Geisel School of Medicine, Dartmouth College , Hanover , NH , USA .
Jason H
JH
Moore
f Josephine Bay Paul Center, Marine Biological Laboratory , Woods Hole , MA , USA , and.
Hilary G
HG
Morrison
f Josephine Bay Paul Center, Marine Biological Laboratory , Woods Hole , MA , USA , and.
Mitchell L
ML
Sogin
c Department of Epidemiology , Geisel School of Medicine, Dartmouth College , Hanover , NH , USA .
Muhammad
M
Zain-Ul-Abideen
g Division of Neonatology, Department of Pediatrics , Dartmouth-Hitchcock Medical Center , Lebanon , NH , USA.
Juliette C
JC
Madan
D000900:Anti-Bacterial Agents / Q000009:adverse effects; D016000:Cluster Analysis; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008137:Longitudinal Studies; D011247:Pregnancy; D011248:Pregnancy Complications / Q000382:microbiology; D011297:Prenatal Exposure Delayed Effects / Q000382:microbiology*; D011446:Prospective Studies
D000900:Anti-Bacterial Agents
Antibiotics; PPPROM; chorioamnionitis; microbiome; obstetrical complications; obstetrical interventions; prematurity