Clostridiales correlate with intestinal barrier maturation in preterm infants

Intestinal barrier immaturity, or “leaky gut,” is the proximate cause of susceptibility to necrotizing enterocolitis (NEC) in preterm neonates. However, the impact of the intestinal microbiota development on intestinal mucosal barrier integrity has not yet been evaluated in the preterms, a high-risk population for NEC and many other health issues. In this study, we investigated a longitudinally sampled cohort of 38 preterm infants with gestational age <33 week during the first two weeks of life. We characterize fecal microbiota at day 1, 8, and 15, and associate with measurement of intestinal permeability (IP) by urinary detection of orally administered sugar probes, lactulose and rhamnose. Rapid decrease in IP indicating maturation of intestinal barrier function correlated with significant increase in community diversity and alteration in community composition and structure. In particular, increasing abundance in members of the Clostridiales was significantly associated with low IP at all time points. Clostridiales were also associated with neonatal factors previously identified to promote infant intestinal barrier maturation, including early introduction of breast milk feeding (< day 2), time to full breast milk feeding (< day 10), shorter period of antibiotic exposure (< 4 days), and later gestational age (<= 28 wk). Metagenomic and metatranscriptomic analyses of the fecal microbiome revealed that Clostridiales is highly transcriptionally active along with members of the Bifidobacterium. The results suggest that neonatal factors favor the early colonization of the gut microbiota by members of the Clostridiales which altogether are associated with improved intestinal barrier in preterm infants. The translational aspect of the study could lead to novel strategy to promote intestinal barrier maturation in preterm infants and potentially lower the risk to NEC.