NADPH oxidases and ROS signaling in the gastrointestinal tract.

Reactive oxygen species (ROS), initially categorized as toxic by-products of aerobic metabolism, have often been called a double-edged sword. ROS are considered indispensable when host defense and redox signaling is concerned and a threat in inflammatory or degenerative diseases. This generalization does not take in account the diversity of oxygen metabolites being generated, their physicochemical characteristics and their production by distinct enzymes in space and time. NOX/DUOX NADPH oxidases are the only enzymes solely dedicated to ROS production and the prime ROS producer for intracellular and intercellular communication due to their widespread expression and intricate regulation. Here we discuss new insights of how NADPH oxidases act via ROS as multifaceted regulators of the intestinal barrier in homeostasis, infectious disease and intestinal inflammation. A closer look at monogenic VEOIBD and commensals as ROS source supports the view of H2O2 as key beneficial messenger in the barrier ecosystem.