Lactobacillus acidophilus induces a strain-specific and toll-like receptor-2 dependent enhancement of intestinal epithelial tight junction barrier and protection against intestinal inflammation.

Abstract

Defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. The purpose of this study was to identify probiotic bacterial species/strain that induces a rapid and sustained enhancement of intestinal TJ barrier and protects against the development of intestinal inflammation by targeting the TJ barrier. Following high-throughput screening of over 20 Lactobacillus and other probiotic bacterial species/strains, a specific strain of Lactobacillus acidophilus (LA) was found to uniquely produce a marked enhancement of intestinal TJ barrier. This particular strain of LA, referred to LA1, attached to the apical membrane surface of intestinal epithelial cells in a Toll-like receptor-2 (TLR-2) dependent manner and caused a rapid increase in enterocyte TLR-2 membrane expression and TLR-2/TLR-1 and TLR-2/TLR-6 hetero-complex dependent enhancement in intestinal TJ barrier function. The LA1 oral administration also caused a rapid enhancement in mouse intestinal TJ barrier, protected against dextran sodium sulfate (DSS)-increase in intestinal permeability, and prevented the DSS-induced colitis in a TLR-2- and intestinal TJ barrier-dependent manner. In conclusion, we show for the first time that a specific strain of LA causes a strain-specific enhancement of intestinal TJ barrier through a novel mechanism involving TLR-2 receptor complex and protects against the DSS-induced colitis by targeting the intestinal TJ barrier.