title: Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia.
abstract: OBJECTIVE
  Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD.
  
  
  METHODS
  Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry.
  
  
  RESULTS
  Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found.
  
  
  CONCLUSIONS
  These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, , Leuven, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vanheel
authors.forename: Maria
authors.initials: M
authors.lastname: Vicario
authors.forename: Tim
authors.initials: T
authors.lastname: Vanuytsel
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.forename: Cristina
authors.initials: C
authors.lastname: Martinez
authors.forename: Åsa V
authors.initials: ÅV
authors.lastname: Keita
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pardon
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
authors.forename: Johan D
authors.initials: JD
authors.lastname: Söderholm
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.forename: Ricard
authors.initials: R
authors.lastname: Farré
mesh_terms: D000293:Adolescent; D000328:Adult; D001530:Belgium; D015153:Blotting, Western; D004386:Duodenum / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004415:Dyspepsia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017097:Electric Impedance; D005260:Female; D005455:Fluorescent Antibody Technique; D064368:Healthy Volunteers; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism*; D055815:Young Adult
keywords: DUODENAL MUCOSA; FUNCTIONAL DYSPEPSIA; INFLAMMATION