Developmental maturation of intestinal junctional complexes in preterm infants

Preterm infants are prone to gastrointestinal complications such as infectious diseases and necrotizing enterocolitis, which are associated with intestinal inflammation and increased intestinal permeability. Intestinal epithelial barrier (IEB) function is known to be immature in preterm neonates; however, our understanding of how the IEB develops - particularly the formation of junctional complexes - remains limited. Here, we analyzed intestinal tissue specimens from healthy resection margins of six very immature preterm infants who underwent bowel resection due to focal intestinal perforation (at the chronological age of 25 to 28 weeks' gestation), and compared the composition of tight junctions, adherens junctions and desmosomes to that of adults. Using immunostaining, our observations show, that tight junction proteins Claudin-2, Claudin-3 and Occludin, adherens junction proteins E-cadherin and β-Catenin as well as desmosomal proteins Plakoglobin and Plakophilin-2 appeared as mature as in adults as early as 25 weeks' gestation. However, Claudin-1, -4 and -5, as well as ZO-1 staining patterns increased and became more defined with increasing gestational age, suggesting junctional maturation during gestational week 26 and 27. Desmosomal protein Desmocollin-2 was increased until 26 weeks' gestation whereas Desmoglein-2 and Desmoplakin expression was immature at 28 weeks' gestation compared to the expression in adults. Our study provides the first sequential characterization of junctional protein maturation across all major IEB components early in life in human samples. These findings may help identify key mechanisms underlying intestinal barrier-associated pathologies in preterm infants.