Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense.

The gut contains the bulk of the body's serotonin (5-hydroxytryptamine, 5-HT); nevertheless, the physiological role that enteric 5-HT plays has not been determined. 5-HT is linked to gastrointestinal (GI) motility; increased intraluminal pressure causes enterochromaffin (EC) cells to secrete 5-HT, which stimulates intrinsic primary afferent neurons that initiate peristaltic reflexes. 5-HT is also an enteric neurotransmitter. Surprisingly, deletion of tryptophan hydroxylase-1 (TPH1), upon which 5-HT biosynthesis in EC cells depends, does not alter constitutive GI motility, whereas deletion of TPH2, upon which biosynthesis of neuronal 5-HT depends, slows intestinal transit and accelerates gastric emptying. TPH1 deletion, however, protects mice from experimental inflammation; 5-HT potentiation and TPH2 deletion each make inflammation more severe. Neuronal 5-HT is neuroprotective and recruits stem cells to give rise to new enteric neurons in adult mice. Mucosal 5-HT, therefore, may mobilize inflammatory effectors, which protect the gut from invasion, whereas neuronal 5-HT shields enteric neurons from inflammatory damage.