Modulation of gut stem cell dynamics by commensal bacteria‐induced ROS generation

Commensal bacteria exhibit positive influences on intestinal homeostasis and restitution following injury. However, the molecular mechanism(s) and cell signaling pathways that mediate these beneficial effects remain uncharacterized. Recently, multiple lines of investigation have shown that rapid cellular generation of reactive oxygen species (ROS) in response to commensal bacteria and/or their products activate cell signaling pathways through the oxidation of critical cysteine residues within regulatory proteins. Using conventional or germ‐free Drosophila gut as a model, we show that commensal bacteria‐induced ROS generation potentiates cellular proliferation and differentiation. Mechanistically, we constitutively activated or suppressed ROS generation within the intestinal stem cell niche by genetic or pharmacologic methods. Constitutive ROS generation within enteric stem cells promoted cellular differentiation, whereas suppressing ROS inhibited differentiation. Furthermore, suppressing ROS significantly increased the numbers of undifferentiated cells within the stem cell niche. Together, these data show that signaling pathways that control stem‐cell growth and differentiation within the gut are sensitive to the cell's redox state, and may be modulated by commensal bacterial‐induced ROS.