Commensal Lactobacillus modulate ROS‐dependent cytoprotective gene expression in intestinal epithelia

Abstract

A growing body of data has emerged showing that members of the gut microbiota are essential for the normal physiology and homeostasis of the intestine. However, the molecular basis for these processes are not well understood. In this study, we describe a novel role for the commensal bacterium Lactobacillus in intestinal cytoprotection. We show that this bacterial genus specifically induces cellular reactive oxygen species (ROS) in both Drosophila and murine guts. This ROS induction in turn stimulates the redox‐sensitive Nrf2 pathway and leads to consequent ARE (Antioxidant Response Element)‐dependent cytoprotective gene expression. Nrf2/ARE pathway mediated cytoprotection is well established in many tissues, but its stimulation by gut bacteria is completely unrecognized. Using Nrf2 knockout Drosophila and mice, we demonstrate that Nrf2 is required for protection against a variety of intestinal insults. Together, these data show that gut microbial stimulated ROS generation modulates the Nrf2 signaling pathway thus maintaining intestinal epithelial homeostasis and cytoprotection, and that this effect is evolutionarily conserved.