Shift work, which refers to work schedules outside the hours of 7AM and 6PM, is a global practice employed in several industries. While being an essential part of the workforce, decades of research has identified shift workers as a vulnerable group at high risk for several chronic diseases associated with weakened immunity. The poor health outcomes of this group are linked to disruptions of the biological clock, which coordinates physiological processes and behaviors with the 24-hour environment light cycle. Light signals entering the eye are processed by the central clock in the brain and used to coordinate biological processes in other organs with the light cycle. However, more research is needed to understand the specific cellular mechanisms linking the clock to immune functions throughout the body. My thesis seeks to address this knowledge gap within the context of gut health by uncovering the pathways responsible for the rhythmic production of antimicrobial proteins in the small intestine. These proteins are essential for the gut’s defense against gastrointestinal pathogens.