Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier.
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.
Host-Microbe Interactomics Group, Univ. of Wageningen, P.O. Box 338, 6700 AH, Wageningen, The Netherlands. jerry.wells@wur.nl
Jurgen
J
Karczewski
Freddy J
FJ
Troost
Irene
I
Konings
Jan
J
Dekker
Michiel
M
Kleerebezem
Robert-Jan M
RJ
Brummer
Jerry M
JM
Wells
D000328:Adult; D018938:Caco-2 Cells; D018592:Cross-Over Studies; D019610:Cytoprotection; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D048191:Lactiplantibacillus plantarum / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D062793:Occludin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D062826:Zonula Occludens-1 Protein