Lactobacilli Modulate Epithelial Cytoprotection through the Nrf2 Pathway

An optimal gut microbiota influences many beneficial processes in the metazoan host. However, the molecular mechanisms that mediate and function in symbiont-induced host responses have not yet been fully characterized. Here, we report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. These data show that the xenobiotic-inducible Nrf2 pathway participates as a signaling conduit between the prokaryotic symbiont and the eukaryotic host. Indeed, our data imply that the capacity of lactobacilli to induce redox signaling in epithelial cells is a highly conserved hormetic adaptation to impel cellular conditioning to exogenous biotic stimuli. These data also highlight the role the microbiota plays in eukaryotic cytoprotective pathways and may have significant implications in the characterization of a eubiotic microbiota. [Display omitted] •Commensal lactobacilli activate the xenobiotic responsive Nrf2 pathway•Nrf2 pathway activation upregulates cytoprotective genes in both Drosophila and mice•Nrf2 target genes protect against environmental stresses•Lactobacilli transduce cytoprotective effects via Nrf2 pathway activation Jones et al. report that the commensal gut bacterial taxa lactobacilli are able to mediate beneficial cytoprotective effects in the gut of both flies and mice. These highly conserved events are mediated by ROS-dependent activation of the Nrf2 xenobiotic pathway and conserved effector genes.