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Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

ABSTRACT: Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

SUBMITTER: Vanheel H

PROVIDER: S-EPMC7562901 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

Vanheel Hanne H Vicario Maria M Beeckmans Dorien D Cocca Silvia S Wauters Lucas L Accarie Alison A Toth Joran J Rodewald Hans-Reimer HR De Hertogh Gert G Matteoli Gianluca G Boeckxstaens Guy G Tack Jan J Farre Ricard R Vanuytsel Tim T

Scientific reports 20201015 1

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high re ...[more]

PMID: 33060783

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Project description:Background & aimsMast cells are believed to contribute to the development of eosinophilic gastrointestinal disorders (EGIDs). We quantified mast cells and eosinophils in biopsy specimens from patients with EGIDs and without known esophageal or gastrointestinal disease to investigate associations between these cell types and EGID and its features.MethodsWe conducted a retrospective study of patients with EGID (n = 52) and of children and adults who underwent upper endoscopy and were found to have no evidence of gastrointestinal or systemic conditions (n = 123). We re-reviewed archived gastric and duodenal biopsy specimens to quantify mast cells (by tryptase immunohistochemistry) and eosinophils. We calculated the specificity of cell count thresholds for identification of patients with EGIDs and evaluated the correlation between mast cell and eosinophil counts and clinical and endoscopic features.ResultsIn the gastric biopsy specimens from patients without esophageal or gastrointestinal diseases, the mean mast cell count was 18.1 ± 7.2 cells per high-power field (hpf), and the peak mast cell count was 21.9 ± 8.2 cells/hpf. In the duodenal biopsy specimens from patients without esophageal or gastrointestinal diseases, the mean mast cell count was 23.6 ± 8.1 cells/hpf and the peak mast cell count was 28.1 ± 9.3 cells/hpf. The mean and peak eosinophil counts in gastric biopsy specimens from patients without disease were 3.8 ± 3.6 eosinophils/hpf and 5.8 ± 5.0 eosinophils/hpf; the mean and peak eosinophil counts in duodenal biopsy specimens were 14.6 ± 8.9 eosinophils/hpf and 19.5 ± 11.0 eosinophils/hpf. A mean count of 20 eosinophils/hpf in gastric biopsy specimens or 30 eosinophils/hpf in duodenal biopsy specimens identified patients with EGIDs with high specificity. Gastric and duodenal biopsy specimens from patients with EGIDs had significant increases in mean mast cell counts compared with biopsy specimens from patients without EGIDs. There was a correlation between mean mast cell and eosinophil counts in duodenal biopsy specimens (R = 0.47; P = .01). The mean mast cell and eosinophil counts did not correlate with symptoms or endoscopic features of EGIDs.ConclusionsWe identified thresholds for each cell type that identified patients with EGIDs with 100% specificity. The increased numbers of mast cells and eosinophils in gastric and duodenal tissues from patients with EGIDs supports the concept that these cell types are involved in pathogenesis. However, cell counts are not associated with symptoms or endoscopic features of EGIDs.

Dataset Information

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

Publications

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

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