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 hours by means of a feeding catheter. Administration of L. plantarum significantly increased tissue staining of the scaffold protein ZO-1 and trans-membrane protein occludin in the vicinity of the tight junctions (TJ) structures which form a paracellular seal between cells of the epithelium. The effects of L. plantarum on ZO-1 were also observed using an in vitro model of the human epithelium but the effects on occludin were minor compared to those seen in vivo. L. plantarum was shown to activate human TLR2 signaling and treatment of Caco-2 monolayers with the TLR2 agonist PCSK, significantly increased fluorescent staining of occludin. Pre-treatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the barrier dysfunction caused by phorbol ester-induced dislocation of ZO-1 and occludin. Taken together these results suggest that TLR2 signaling at the epithelial surface would also have a protective effect on barrier disruption in humans. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial TJ integrity has important implications for understanding probiotic mechanisms and the control of intestinal homeostasis.