Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure

Gastroenterology. 2002 Nov;123(5):1607-15. doi: 10.1053/gast.2002.36578.


Background & aims: Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability.

Methods: Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers.

Results: Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex.

Conclusions: This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Physiological Phenomena*
  • Caco-2 Cells
  • Cell Line
  • Cholera Toxin / metabolism*
  • Enterobacteriaceae / physiology
  • Escherichia coli / physiology
  • Fluorescent Antibody Technique, Direct
  • Haptoglobins
  • Humans
  • Ileum / microbiology
  • Immunoblotting
  • Intestine, Small / metabolism*
  • Intestine, Small / microbiology*
  • Macaca mulatta
  • Membrane Proteins / metabolism
  • Organ Culture Techniques
  • Permeability
  • Phosphoproteins / metabolism
  • Protein Precursors
  • Rabbits
  • Rats
  • Rats, Wistar
  • Time Factors
  • Zonula Occludens-1 Protein


  • Haptoglobins
  • Membrane Proteins
  • Phosphoproteins
  • Protein Precursors
  • TJP1 protein, human
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • zonulin
  • Cholera Toxin