Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants.

Bing Ma,Mike Humphrys,Hongqiu Yang,Jacques Ravel,Rose M Viscardi,Pawel Gajer,Elias Mccomb,Adora C Okogbule-Wonodi,Alessio Fasano

doi:10.3389/fmicb.2018.02755

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.

Highlights

The intestinal mucosa paracellular trafficking of macromolecules is controlled by a competent epithelial barrier (Lee, 2015)
Neonatal factors previously identified to promote intestinal barrier maturation, including early exclusive breastmilk feeding and less 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
We further observed neonatal factors previously identified to promote intestinal barrier maturation, including early exclusive breastmilk feeding and shorter duration antibiotic exposure that are associated 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

Summary

Introduction

The intestinal mucosa paracellular trafficking of macromolecules is controlled by a competent epithelial barrier (Lee, 2015). The colonization with microorganisms starts at birth and undergoes rapid shifts in composition and structure as the host matures over time (Koenig et al, 2011; Sharon et al, 2013; Grier et al, 2017; de Muinck and Trosvik, 2018) These microorganisms perform essential functions mechanistically linked to the immune. Intestinal Microbiome and Permeability Preterm system development, nutrient acquisition and energy regulation, opportunistic pathogens suppression, as well as intestinal barrier competency, which includes epithelial metabolism, proliferation and survival, mucin and antimicrobial compound production, and cell-cell communication signaling molecule secretion (Neish, 2009; Belkaid and Hand, 2014; Yu et al, 2016). NEC is a life-threatening, gastrointestinal emergency affecting approximately 7–10% of preterm neonates with mortality as high as 30–50% (Guner et al, 2009) In this condition, bacteria cross the intestinal wall leading to local and systemic infection and inflammation, and bowel wall necrosis and perforation. It is critical to characterize the preterm infant intestinal microbiota to identify dysbiotic states associated with increased intestinal leakiness, as well as beneficial bacteria associated with improved intestinal barrier function, for subsequent stratification of early diagnosis, early intervention and primary prevention of leaky gut and its sequelae

Methods

Results

Discussion

Conclusion