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

Rahzi El Asmar, Pinaki Panigrahi, Penelope Bamford, Irene Berti, Tarcisio Not, Giovanni V. Coppa, Carlo Catassi, Alessio Fasano

Research output: Contribution to journalArticlepeer-review

285 Scopus citations


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 microsnapwells. 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.

Original languageEnglish (US)
Pages (from-to)1607-1615
Number of pages9
Issue number5
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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