Host-Derived Reactive Oxygen Species in the Gut Epithelium: Defence Mechanism and Target of Bacterial Subversion

Host physical, chemical, and immune responses constitute well-established defences against bacterial invasion. Recent studies have highlighted the critical role of cellular mechanisms, particularly the production of reactive oxygen species (ROS) in antibacterial defence. This review focuses on ROS generation by mammalian intestinal epithelial cells (IECs) and investigates whether ROS production is host-driven to eliminate bacteria or manipulated by bacteria to suppress or exploit ROS for enhanced internalisation. We examine the activation mechanisms of the NADPH oxidase (NOX) enzyme complex and the resulting ROS production in IECs, which, unlike professional phagocytes, lack the ability to engulf bacteria. The downstream effects of NOX-mediated ROS signalling are discussed in detail. Additionally, we explore the dynamic interplay between host and pathogen, with particular attention to how bacterial infection may disrupt or hijack host NOX-mediated ROS responses. The review concludes with key experimental considerations and outlines future directions in this evolving field. Overall, we present ROS as a double-edged sword, an essential antimicrobial effector that is also susceptible to bacterial subversion, highlighting its potential as a target in novel antimicrobial strategies.