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Impaired gastric mucosal integrity identified by confocal endomicroscopy in Helicobacter pylori-negative functional
Rui Ji1, Peng Wang1, Guan-Jun Kou1
1Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.
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.
Insights
Functional dyspepsia (FD) is linked to impaired gastric barrier function. Increased mast cells in the stomach correlate with this heightened permeability, suggesting a new therapeutic target for FD.
Area of Science:
- Gastroenterology
- Pathophysiology
- Inflammation research
Background:
- Functional dyspepsia (FD) pathogenesis may involve low-grade inflammation.
- Altered gastric permeability is hypothesized to contribute to FD onset and persistence.
Purpose of the Study:
- To evaluate gastric mucosal integrity and mast cell counts in FD patients.
- To investigate the relationship between gastric permeability and mast cell numbers in FD.
Main Methods:
- Probe-based confocal endomicroscopy with intravenous fluorescein was used to assess paracellular leakage and cell shedding in 58 FD patients, 20 H. pylori-positive controls, and 20 H. pylori-negative healthy controls.
- Quantitative immunohistochemistry was employed to identify and quantify mast cells in mucosal biopsies.
Main Results:
- FD patients exhibited significantly higher paracellular permeability scores compared to healthy controls (P=.006).
- Mast cell numbers were significantly increased in FD patients versus healthy controls (P<.001).
- Gastric permeability positively correlated with mast cell numbers in FD patients (rs=.6588, P<.0001).
Conclusions:
- FD patients demonstrate impaired gastric barrier function.
- Increased mast cell infiltration and heightened gastric permeability represent a potential pathophysiological mechanism and therapeutic target for FD.
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