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

Am J Physiol Gastrointest Liver Physiol. 2010 Jun;298(6):G851-9. doi: 10.1152/ajpgi.00327.2009. Epub 2010 Mar 11.


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 Pam(3)-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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Caco-2 Cells
  • Cross-Over Studies
  • Cytoprotection
  • Duodenum / cytology
  • Duodenum / metabolism
  • Epithelial Cells / metabolism*
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Lactobacillus plantarum / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Occludin
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Signal Transduction
  • Tight Junctions / genetics
  • Tight Junctions / metabolism*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Zonula Occludens-1 Protein


  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • TJP1 protein, human
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Zonula Occludens-1 Protein