title: Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism.
abstract: OBJECTIVE
  Intestinal permeability and psychological stress have been implicated in the pathophysiology of IBD and IBS. Studies in animals suggest that stress increases permeability via corticotropin-releasing hormone (CRH)-mediated mast cell activation. Our aim was to investigate the effect of stress on intestinal permeability in humans and its underlying mechanisms.
  
  
  METHODS
  Small intestinal permeability was quantified by a 2 h lactulose-mannitol urinary excretion test. In a first study, 23 healthy volunteers were subjected to four different conditions: control; indomethacin; public speech and anticipation of electroshocks. In a second study, five test conditions were investigated in 13 volunteers: control; after pretreatment with disodium cromoglycate (DSCG); administration of CRH; DSCG+CRH and DSCG+public speech.
  
  
  RESULTS
  Indomethacin, as a positive comparator (0.071±0.040 vs 0.030±0.022; p<0.0001), and public speech (0.059±0.040; p<0.01), but not the shock protocol increased intestinal permeability. Similarly, salivary cortisol was only increased after public speech. Subgroup analysis demonstrated that the effect of public speech on permeability was only present in subjects with a significant elevation of cortisol. CRH increased the lactulose-mannitol ratio (0.042±0.021 vs 0.028±0.009; p=0.02), which was inhibited by the mast cell stabiliser DSCG. Finally, intestinal permeability was unaltered by public speech with DSCG pretreatment.
  
  
  CONCLUSIONS
  Acute psychological stress increases small intestinal permeability in humans. Peripheral CRH reproduces the effect of stress and DSCG blocks the effect of both stress and CRH, suggesting the involvement of mast cells. These findings provide new insight into the complex interplay between the central nervous system and GI function in man.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium Department of Gastroenterology, Leuven University Hospitals, Leuven, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Vanuytsel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Sander
authors.initials: S
authors.lastname: van Wanrooy
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vanheel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanormelingen
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Verschueren
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Houben
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Shadea
authors.initials: S
authors.lastname: Salim Rasoel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Joran
authors.initials: J
authors.lastname: Tόth
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Lieselot
authors.initials: L
authors.lastname: Holvoet
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Ricard
authors.initials: R
authors.lastname: Farré
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium Department of Gastroenterology, Leuven University Hospitals, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Boeckxstaens
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium Department of Gastroenterology, Leuven University Hospitals, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
mesh_terms: D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004597:Electroshock / Q000523:psychology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007213:Indomethacin; D007421:Intestine, Small / Q000503:physiopathology*; D007792:Lactulose / Q000652:urine; D008297:Male; D008353:Mannitol / Q000652:urine; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D010539:Permeability / Q000187:drug effects; D012463:Saliva / Q000378:metabolism; D013060:Speech / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology* / Q000652:urine; D055815:Young Adult
chemical_list: D008353:Mannitol; D007792:Lactulose; D003346:Corticotropin-Releasing Hormone; D004205:Cromolyn Sodium; D006854:Hydrocortisone; D007213:Indomethacin
keywords: Epithelial Barrier; Inflammatory Bowel Disease; Irritable Bowel Syndrome; Mast Cells; Stress