Quiet but powerful: the role of the enteric nervous system in the pathophysiology of gastrointestinal disease (214.1)

The enteric nervous system (ENS) is large, complex, and uniquely able to function independently of the CNS. The ENS is also essential and, when defective, causes disorders of gastrointestinal (GI) motility, secretion, inflammation, and/or infection. Although the ENS is neural crest‐ and the CNS is neural tube‐derived, many developmental processes and molecules are common to both systems. Disruptions of GI function thus frequently occur together with cognitive/behavioral abnormalities as components of disorders (such as Parkinson's and autism) that affect both ENS and CNS. Serotonin (5‐HT) is a molecule that both gut and CNS express. Enteric 5‐HT is stored in enteroendocrine (EC) cells and neurons and participates in peristaltic reflexes, secretion, crypt cell proliferation, GI inflammation, neurotransmission, ENS development, and neurogenesis. EC cell and neuronal 5‐HT biosynthesis depend, respectively on tryptophan hydroxylase 1 (TPH1) and TPH2. A high affinity 5‐HT transporter (SERT) inactivates both mucosal and neuronal 5‐HT. Selective deletion of the TPH’s has enabled roles of EC cell and neuronal 5‐HT to be distinguished. Studies of mice that lack SERT, or which express SERT mutations associated with human disorders, confirm that enteric 5‐HT is multifunctional and link 5‐HT to the pathogenesis of GI manifestations of autism and functional GI disease.