Lactobacillus rhamnosus GG accelerates intestinal barrier maturation in developing mice through induction of tight junction proteins

Necrotizing enterocolitis (NEC) is a devastating disease affecting preterm infants. Probiotics may prevent NEC by strengthening the immature epithelial barrier of the preterm gut. Tight junctions (TJ), comprised of transmembrane Claudin proteins (Cldn) that seal the paracellular space, are a vital part of the intestinal epithelial barrier. However, how probiotics modulate Cldn expression to promote barrier maturation and prevent NEC in the immature gut is unknown. After screening the ontogeny of TJ protein expression by qRT‐PCR in the neonatal murine ileum, we identified Cldn 3 and 7 as two TJ proteins that peak in expression at 3 weeks of life. Western blotting and confocal microscopy confirmed Cldn protein expression and localization also matured at 3 weeks. These changes temporally correlated with functional maturation of the mucosal barrier as assessed by FITC‐dextran permeability. Both MyD88 null and antibiotic‐raised mice demonstrated immature Cldn 3 and 7 expression and increased intestinal permeability when compared to wild type and conventionally raised mice, respectively. In contrast, mice gavage‐fed Lactobacillus rhamnosus GG demonstrated increased Cldn 3 and 7 expression and accelerated maturation of gut barrier function. These results suggest that both commensal and probiotic bacteria induce maturation of the intestinal barrier by promoting increased expression of key Cldn proteins.