Intestinal barrier dysfunction in human necrotizing enterocolitis.

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±1.65Ω/cm in NEC specimens, 23.36±1.48Ω/cm at resection margin, and 46.48±5.65Ω/cm in controls. Average flux of permeability marker mannitol was 0.23±0.06μMol/cm per h in NEC, 0.04±0.01 μMol/cm per h at resection margin, and 0.017±0.004 μMol/cm 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.