Impaired gastric mucosal integrity identified by confocal endomicroscopy in Helicobacter pylori-negative functional dyspepsia

Background: Low-grade inflammation may be involved in the pathogenesis of functional dyspepsia (FD). We hypothesis that altered gastric permeability is involved in the onset and persistence of this disorder. Therefore, our aim was to evaluate gastric mucosal integrity and mast cell numbers in patients with FD. Methods: We enrolled 58 patients with FD fulfilling the Rome III criteria (H Pylori negative), 20 inflammatory control subjects (H Pylori positive), and 20 healthy controls (H Pylori negative). Probe-based confocal endomicroscopy was performed using intravenous fluorescein to assess the paracellular fluorescein leakage and cell shedding. Mast cells were identified with quantitative immunohistochemistry on mucosal biopsies. Key Results: Endomicroscopic score of paracellular permeability was significantly higher in H pylori-negative FD patients compared with healthy controls (1.45 +/- 1.27 vs 3.69 +/- 3.18, P =.006). However, FD patients and healthy controls did not show differences in cell shedding score (0.75 +/- 0.79 vs 1.29 +/- 1.14, P =.069). Mast cell numbers were significantly increased compared with healthy control samples (18.91 +/- 5.47 vs 14.1 +/- 3.88, P <.001). The magnitude of increase in permeability was positively correlated with mast cell numbers of FD patients (rs =.6588, P <.0001), but not dyspepsia symptom scores. Conclusion and Inferences: Impaired gastric barrier function is present in FD patients. This might provide a new pathophysiological mechanism and therapeutical target in FD.