title: Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome.
abstract: BACKGROUND
  Alterations in serotonergic (5-HT) metabolism and/or intestinal integrity have been associated with irritable bowel syndrome (IBS).
  
  
  OBJECTIVE
  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.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Keszthelyi
authors.forename: F J
authors.initials: FJ
authors.lastname: Troost
authors.forename: D M
authors.initials: DM
authors.lastname: Jonkers
authors.forename: H M
authors.initials: HM
authors.lastname: van Eijk
authors.forename: P J
authors.initials: PJ
authors.lastname: Lindsey
authors.forename: J
authors.initials: J
authors.lastname: Dekker
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.forename: A A M
authors.initials: AA
authors.lastname: Masclee
mesh_terms: D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D007422:Intestines / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D055815:Young Adult
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan