Heat-killed yogurt-containing lactic acid bacteria prevent cytokine-induced barrier disruption in human intestinal Caco-2 cells

Probiotics have been proven to play a protective role against gut barrier disruption induced by enteroinvasive pathogens and chemical substances. To test the hypothesis that a heat-inactivated multi-strain of yogurt-containing lactic acid bacteria (Mix-LAB) (Lactobacillus bulgaricus, Streptococcus thermophilus, Lactobacillus acidophilus) could prevent epithelial barrier dysfunction induced by inflammatory cytokines, human intestinal Caco-2 cell monolayers were cultured for 72 h with cytomix (interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta) alone and in combination with graded concentrations of heat-inactivated Mix-LAB (10(7),10(8),10(9)/ml). After incubation for 72 h, cytomix decreased the transepithelial electrical resistance (TEER) and increased the paracellular permeability of Caco-2 monolayers to fluoresceinated dextran (molecular weight 376 Da), which was inhibited by the pretreatment of heat-inactivated Mix-LAB under culture conditions. This protective effect of heat-inactivated Mix-LAB on reduced TEER and increased paracellular permeability was concentration-dependent, rising to statistically significant levels for concentrations equal to or greater than 10(7) /ml after 72-h incubation and 10(8) /ml after 48-h incubation. Cytomix altered the expression and distribution of the tight junction proteins ZO-1 and occludin, but this effect was prevented by the heat-inactivated Mix-LAB. These data suggest that heat-inactivated yogurt-containing Mix-LAB plays a protective role in proinflammatory cytokine-induced intestinal epithelial barrier dysfunction.