Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

J. Karczewski, F.J. Troost, I. Konings, J. Dekker, M. Kleerebezem, R.J. Brummer, J. Wells

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Abstract

Lactobacillus plantarum, a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam3-Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis
Original languageEnglish
Pages (from-to)G851-G859
JournalAmerican Journal of Physiology. Gastrointestinal and Liver Physiology
Volume298
Issue number6
DOIs
Publication statusPublished - 2010

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Keywords

  • inflammatory-bowel-disease
  • necrosis-factor-alpha
  • intestinal permeability
  • kinase-c
  • mucosal integrity
  • probiotics
  • cells
  • rats
  • pathophysiology
  • dysfunction

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