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Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia
  1. Hanne Vanheel1,
  2. Maria Vicario2,3,
  3. Tim Vanuytsel1,
  4. Lukas Van Oudenhove1,
  5. Cristina Martinez2,
  6. Åsa V Keita4,
  7. Nicolas Pardon1,
  8. Javier Santos2,3,
  9. Johan D Söderholm4,5,
  10. Jan Tack1,
  11. Ricard Farré1,3
  1. 1Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
  2. 2Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos II, Madrid, Spain
  4. 4Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  5. 5Department of Surgery, County Council of Östergötland, Linköping, Sweden
  1. Correspondence to Professor Jan Tack, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Herestraat 49, box 701, Leuven 3000, Belgium; jan.tack{at}med.kuleuven.be

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.

Design 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.

  • FUNCTIONAL DYSPEPSIA
  • DUODENAL MUCOSA
  • INFLAMMATION

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