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, Isabelle G. De Plaen

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Whether 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.

Original languageEnglish (US)
Pages (from-to)1595-1606
Number of pages12
JournalAmerican Journal of Pathology
Volume182
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Bergmann, K. R., Liu, S. X. L., Tian, R., Kushnir, A., Turner, J. R., Li, H. L., Chou, P. M., Weber, C. R., & De Plaen, I. G. (2013). Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis. American Journal of Pathology, 182(5), 1595-1606. https://doi.org/10.1016/j.ajpath.2013.01.013