Anemia is a frequent diagnosis in
critically ill infants, but the clinical implications of severe
anemia in these patients remain unclear. In this study, we examined preweaned mice to investigate the effects of severe
anemia during early infancy on gut mucosal permeability. C57BL/6 mice were subjected to timed phlebotomy between postnatal days (
P) 2-10 to induce severe
anemia (hematocrits 20%-24%), and intestinal permeability was tracked longitudinally between P10 and P20 as intestine-to-plasma translocation of enteral macromolecules and bacterial translocation. Epithelial junctions were evaluated by electron microscopy, polymerase chain reactions, immunohistochemistry, and/or
enzyme immunoassays on intestinal tissues, Caco-2 intestinal epithelial-like cells, and colonic organoids. Preweaned mouse pups showed an age-related susceptibility to severe
anemia, with increased intestinal permeability to enteral macromolecules (
dextran,
ovalbumin, β-
lactoglobulin) and
luminal bacteria. Electron micrographs showed increased paracellular permeability and ultrastructural abnormalities of the adherens junctions. These findings were explained by the loss of
E-cadherin in epithelial cells, which was caused by destabilization of the
E-cadherin (Cdh1)
mRNA because of
microRNA let-7e-5p binding to the 3'-untranslated region. Severe
anemia resulted in a disproportionate and persistent increase in intestinal permeability in preweaned mice because of the disruption of epithelial adherens junctions. These changes are mediated via
microRNA let-7e-mediated depletion of Cdh1
mRNA.NEW & NOTEWORTHY This research article shows that newborn infants with severe
anemia show an age-related susceptibility to developing increased intestinal permeability to ingested macromolecules. This abnormal permeability develops because of abnormalities in intestinal epithelial junctions caused by a deficiency of the molecule
E-cadherin in epithelial cells. The deficiency of
E-cadherin is caused by destabilization of its
mRNA precursor because of increased expression and binding of another molecule, the
microRNA let-7e-5p, to the
E-cadherin mRNA.