Neural and Glial Contributions to Mucosal Repair in Inflammatory Bowel Disease

Mucosal healing is a central therapeutic goal in inflammatory bowel disease (IBD), yet control of inflammation does not invariably restore a durable and functional epithelium. Neural circuits are positioned to influence this discrepancy because they interact with epithelial, immune, stromal, vascular, and microbial components of the repair niche. However, evidence for neural regulation remains fragmented across studies of innervation, enteric glial cells, guidance cues, neurotransmitters, and neuro-immune signaling. Web of Science and PubMed were searched through October 2026 using terms covering IBD, mucosal repair, neural and glial signaling, and axon guidance; original mechanistic studies were prioritized and assessed by experimental model, cellular source and target, mechanistic intervention, and measured repair outcome. This review distinguishes acute restitution, barrier restoration, structural regeneration, and durable healing, and examines how sensory, autonomic, enteric neuronal, and glial pathways influence these outcomes across disease stages in IBD. It relates each pathway’s cellular source and response to neural perturbation to its disease context and highest measured repair endpoint. Semaphorin, netrin, Slit/Robo, and Eph/ephrin pathways may contribute to spatial organization, although most intestinal studies have not established that these effects depend on neural activity. By integrating repair endpoint, neural causality, disease stage, and cellular context, the review identifies key neural control points and experimental priorities for clinically meaningful translation.