Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants

Abstract

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.

Current understanding of the role of gut dysbiosis in type 1 diabetes

“…Establishment of the human gut microbiome is believed to take place during late prenatal life . A recent study involving 38 preterm infants revealed an association between increased diversity of the neonate gut microbial community during the first 2 weeks after birth and maturation of the gut barrier, indicated by decreased intestinal permeability . Among the bacteria that were found to increase in abundance during this period were members of the Clostridiales and Bifidobacterium .…”

“…A recent study involving 38 preterm infants revealed an association between increased diversity of the neonate gut microbial community during the first 2 weeks after birth and maturation of the gut barrier, indicated by decreased intestinal permeability . Among the bacteria that were found to increase in abundance during this period were members of the Clostridiales and Bifidobacterium . Another recent multicenter study by The Environmental Determinants of Diabetes in the Young (TEDDY) involving 903 children aged 3‐46 months showed that the developing gut microbiome undergoes three distinct phases: developmental, transitional, and stable .…”

“…Breast milk feeding was found to be the most significant factor associated with the microbiome structure during first year of life, being associated with higher levels of Bifidobacterium species ( B. breve and B. bifidum ), and its cessation resulted in faster maturation of the gut microbiome, indicated by a higher abundance of Firmicutes . The timing of first breast milk feeding is also associated with changes in the properties of the gut barrier . Exclusive breast milk feeding by Day 10 in preterm infants is associated with an abundance of Clostridiales with decreased permeability of the gut barrier .…”

“…The timing of first breast milk feeding is also associated with changes in the properties of the gut barrier . Exclusive breast milk feeding by Day 10 in preterm infants is associated with an abundance of Clostridiales with decreased permeability of the gut barrier . Conversely, full breast milk feeding achieved after Day 10 was significantly associated with the abundance of Enterobacteriaceae, particularly Klebsiella pneumoniae .…”

“…The gut microbiota exhibit a symbiotic relationship with their host by maintaining the integrity of the intestinal wall, assisting in food digestion, producing vitamins and protecting against the outgrowth of pathogenic organisms . Microbial colonization to the human gut takes place during early life, concomitant with maturation of the gut barrier . By 3 years of age, the microbiome profile exhibits the maturity of adults .…”