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Front Microbiol. 2018 Nov 14;9:2755. doi: 10.3389/fmicb.2018.02755. eCollection 2018.

Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants.

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Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States.
Department of Pediatrics and Child Health, Howard University College of Medicine, Washington, DC, United States.
Department of Pediatrics, Basic, Clinical and Translational Research, MassGeneral Hospital for Children, Boston, MA, United States.
Harvard Medical School, Boston, MA, United States.
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, United States.


Intestinal barrier immaturity, or "leaky gut," is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. However, the impact of intestinal microbiota development on intestinal mucosal barrier maturation has not been evaluated in this population. In this study, we investigated a longitudinally sampled cohort of 38 preterm infants < 33 weeks gestation monitored for intestinal permeability (IP) and fecal microbiota during the first 2 weeks of life. Rapid decrease in IP indicating intestinal barrier function maturation correlated with significant increase in community diversity. In particular, members of the Clostridiales and Bifidobacterium were highly transcriptionally active, and progressively increasing abundance in Clostridiales was significantly associated with decreased intestinal permeability. Further, neonatal factors previously identified to promote intestinal barrier maturation, including early exclusive breastmilk feeding and shorter duration antibiotic exposure, associate with the early colonization of the intestinal microbiota by members of the Clostridiales, which altogether are associated with improved intestinal barrier function in preterm infants.


Bifidobacterium; Clostridiales; breastmilk feeding; intestinal microbiota; intestinal permeability; leaky gut; necrotizing enterocolitis; preterm infant

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