Pain is a significant contributor to disease burden in Inflammatory Bowel Disease (IBD), as nearly half of individuals with ulcerative colitis and Crohn’s disease report persistent intestinal pain. Such pain is generally mediated by nociceptors, peripheral sensory neurons that detect harmful stimuli. The mechanisms leading to nociceptor activation in IBD are poorly understood, and few treatments for chronic pain exist.
Recent evidence suggests that the gut microbiome can regulate pain signaling, yet the specific microbial products involved are largely unknown. We hypothesize that microbiome-derived metabolites play major roles in influencing intestinal nociceptors and shaping pain responses in IBD. The goal of this project is to comprehensively delineate such roles. For this purpose, we have developed an innovative workflow that integrates human iPSC-derived sensory neurons and a curated library of microbial chemicals, using which we will identify compounds that activate or inhibit the activities of nociceptors. We will then test how these chemicals affect pain in animal models of IBD and define the pathways by which they act on neurons. By identifying gut microbial signals that exacerbate or alleviate pain, our research will lay the foundations of novel biomarkers and therapies to treat pain in IBD.
