• Am. J. Pathol. · May 2013

    Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis.

    • Kelly R Bergmann, Shirley X L Liu, Runlan Tian, Anna Kushnir, Jerrold R Turner, Hong-Lin Li, Pauline M Chou, Christopher R Weber, and Isabelle G De Plaen.
    • Division of Neonatology, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
    • Am. J. Pathol. 2013 May 1; 182 (5): 1595-606.

    AbstractWhether intestinal barrier disruption precedes or is the consequence of intestinal injury in necrotizing enterocolitis (NEC) remains unknown. Using a neonatal mouse NEC model, we examined the changes in intestinal permeability and specific tight-junction (TJ) proteins preceding NEC and asked whether these changes are prevented by administration of Bifidobacterium infantis, a probiotic known to decrease NEC incidence in humans. Compared with dam-fed controls, pups submitted to the NEC protocol developed i) significantly increased intestinal permeability at 12 and 24 hours (as assessed by 70-kDa fluorescein isothiocyanate-dextran transmucosal flux); ii) occludin and claudin 4 internalization at 12 hours (as assessed by immunofluorescence and low-density membrane fraction immunoblotting); iii) increased claudin 2 expression at 6 hours and decreased claudin 4 and 7 expression at 24 hours; and iv) increased claudin 2 protein at 48 hours. Similar results were seen in human NEC, with claudin 2 protein increased. In mice, administration of B. infantis micro-organisms attenuated increases in intestinal permeability, preserved claudin 4 and occludin localization at TJs, and decreased NEC incidence. Thus, an increase in intestinal permeability precedes NEC and is associated with internalization of claudin 4 and occludin. Administration of B. infantis prevents these changes and reduces NEC incidence. The beneficial effect of B. infantis is, at least in part, due to its TJ and barrier-preserving properties.Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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