Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome

Summary Background Alterations in serotonergic (5‐ HT ) metabolism and/or intestinal integrity have been associated with irritable bowel syndrome ( IBS ). Aims To assess the effects of the precursor of 5‐ HT , 5‐hydroxytryptophan (5‐ HTP ), on mucosal 5‐ HT availability and intestinal integrity, and to assess potential differences between healthy controls and IBS patients. Methods Fifteen IBS patients and 15 healthy volunteers participated in this randomised double‐blind placebo‐controlled study. Intestinal integrity was assessed by dual‐sugar test and by determining the mucosal expression of tight junction proteins after ingestion of an oral bolus of 100 mg 5‐ HTP or placebo. Mucosal serotonergic metabolism was assessed in duodenal biopsy samples. Results 5‐ HTP administration significantly increased mucosal levels of 5‐ HIAA , the main metabolite of 5‐ HT , in both healthy controls (7.1 ± 1.7 vs. 2.5 ± 0.7 pmol/mg, 5‐ HTP vs. placebo, P = 0.02) and IBS patients (20.0 ± 4.8 vs. 8.1 ± 1.3 pmol/mg, 5‐ HTP vs. placebo, P = 0.02), with the latter group showing a significantly larger increase. Lactulose/L‐rhamnose ratios were significantly lower after administration of 5‐ HTP ( P < 0.05) in healthy controls and were accompanied by redistribution of zonula occludens‐1 ( ZO ‐1), pointing to reinforcement of the barrier. In IBS , expression of the tight junction proteins was significantly lower compared to healthy controls, and 5‐ HTP resulted in a further decrease in occludin expression. Conclusions Oral 5‐ HTP induced alterations in mucosal 5‐ HT metabolism. In healthy controls, a reinforcement of the intestinal barrier was seen whereas such reaction was absent in IBS patients. This could indicate the presence of a serotonin‐mediated mechanism aimed to reinforce intestinal barrier function, which seems to dysfunction in IBS patients.