Forkhead Box Protein O1 is Linked to Anti-Inflammatory Probiotic BacteriaActing through Nuclear Factor-úB Pathway

Abstract

Probiotics are widely used to promote health benefits around the world. Nevertheless, the mechanisms whereby probiotics exert its beneficial effect on the host are not well elucidated yet. In an attempt to obtain relevant insights on probiotics mechanisms of action, we studied the probiotic response via Nuclear factor-κB (NF-κB) and Forkhead box protein O1 (FoxO1), two transcription factors that were previously related with probiotic effects. We performed in vitro analysis to activate these transcription factors with Tumor Necrosis Factor alpha (TNFα) and Hydrogen Peroxide (H2O2) stimuli using a set of probiotic strains co-cultured with HT-29 cells. We found three strains, LrBPL8, LcA1 and LaBPL71 capable to reducing the NF-κB activation pathway in an inflammatory context. We also found that LcA1 reduced FoxO1 activation while another strain, IPM C+, increased it after the hydrogen peroxide treatment under the same conditions. Moreover, we described a complex relationship between FoxO1 downstream gene expression and these anti-inflammatory strains. Our results show that more than one pathway could be targeting NF-κB modulation, indicating the complexity of the probiotics’ mechanisms of action. The in vitro data presented here may help to design multi-strain probiotics mix that take advantage of the complementary and synergistic effects that they may induce in the host.