Lactobacilli enhance reactive oxygen species-dependent apoptosis-inducing signaling

H2O2-producing lactobacilli in the vaginal fluid have been suggested to play a potential tumor-preventive role in addition to the control of undesirable microorganisms. As the vaginal fluid also contains a significant concentration of peroxidase that might utilize lactobacilli-derived H2O2 as substrate for HOCl synthesis, a dominant biological role of HOCl in both natural defence systems has been postulated. Our study shows that lactobacillus-derived H2O2 per se is not likely to be beneficial for the vaginal epithelium, as it causes apoptosis nonselectively in nontransformed as well as transformed cells. However, the combination of lactobacilli and peroxidase, i.e. the situation that is actually found in vivo, leads to the conversion of H2O2 to HOCl which does not affect non-malignant cells, as these do not generate extracellular superoxide anions. In contrast, malignant cells, due to their abundant extracellular superoxide anion generation allow the generation of apoptosis-inducing hydroxyl radicals through HOCl/superoxide anion interaction. In total, our data show that the combination of H2O2 -generating lactobacilli and peroxidase causes the selective elimination of malignant cells and thus might contribute to the tumorpreventive potential of lactobacilli. These findings are in good agreement with epidemiological data. The contribution of lactobacilli in this system can be completely mimicked by H2O2-generating glucose oxidase, indicating that it is fully explained by bacterial generation of H2O2.