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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 298; no. 6; pp. G851 - G859
• Main Authors: Karczewski, Jurgen, Troost, Freddy J., Konings, Irene, Dekker, Jan, Kleerebezem, Michiel, Brummer, Robert-Jan M., Wells, Jerry M.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2010
• Subjects: Adult; Caco-2 Cells; Cells; Comparative analysis; Cross-Over Studies; Cytoprotection; Duodenum - cytology; Duodenum - metabolism; dysfunction; Effects; Epithelial Cells - metabolism; epithelium; Gastrointestinal diseases; Homeostasis; Humans; inflammatory-bowel-disease; Intestinal Mucosa - cytology; Intestinal Mucosa - metabolism; intestinal permeability; intestine; kinase-c; Lactobacillus plantarum - physiology; MEDICIN; MEDICINE; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microscopy, Confocal; mucosal integrity; necrosis-factor-alpha; Occludin; pathophysiology; Phosphoproteins - genetics; Phosphoproteins - metabolism; Probiotics; Proteins; rats; Signal Transduction; T cell receptors; Tight Junctions - genetics; Tight Junctions - metabolism; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Zonula Occludens-1 Protein
• ISSN: 0193-1857; 1522-1547; 1522-1547
• DOI: 10.1152/ajpgi.00327.2009

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.