Intestinal barrier dysfunction in human necrotizing enterocolitis

Sarah A. Moore, Prashant Nighot, Cynthia Reyes, Manmeet Rawat, Jason McKee, David Lemon, Joshua Hanson, Thomas Y. Ma

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background Intestinal barrier dysfunction has been implicated in necrotizing enterocolitis (NEC), but has not been directly measured in human NEC. Methods Small intestines removed during surgery were immediately mounted in an Ussing chamber. mRNA expression of tight junction (TJ) proteins was measured with RT-PCR. Results Fifteen infants were included, 5 with NEC and 10 with other diagnoses. Average transepithelial resistance (TER) was 11.61 ± 1.65 Ω/cm2 in NEC specimens, 23.36 ± 1.48 Ω/cm2 at resection margin, and 46.48 ± 5.65 Ω/cm2 in controls. Average flux of permeability marker mannitol was 0.23 ± 0.06 μMol/cm2 per h in NEC, 0.04 ± 0.01 μMol/cm2 per h at resection margin, and 0.017 ± 0.004 μMol/cm2 per h in control tissue (p < 0.05). RT-PCR analysis showed marked decrease in mRNA expression of a TJ protein occludin in NEC affected tissue (p < 0.03 vs. control). Additionally, mRNA expression of myosin light chain kinase (MLCK), an important regulator of TJ permeability, was increased in NEC specimens. Conclusion These studies show for the first time that NEC intestinal tissue have increased intestinal permeability, even at grossly healthy-appearing resection areas. The increase in intestinal permeability in NEC appeared to be related in part to a decrease in occludin and an increase in MLCK expression. Level of evidence Level 2.

Original languageEnglish (US)
Pages (from-to)1907-1913
Number of pages7
JournalJournal of pediatric surgery
Volume51
Issue number12
DOIs
StatePublished - Dec 1 2016

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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