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It is estimated that the adult human gut contains over 500 million neurons ( Functionally, the ENS innervates nearly all functional units within the gutincluding epithelial cells, smooth muscle, interstitial cells of Cajal (ICC), vasculature, and diverse immune cellsenabling it to dynamically sense environmental changes and mount adaptive responses ( Perturbations in ENS signaling compromise epithelial barrier integrity, disrupt immune tolerance, and alter microbiota-host communication, thereby driving colitis pathogenesis through dysregulation of the neuro-immune-microbial axis