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.
Highlights
Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure
Duodenal saline/acid perfusion was performed in 10 healthy volunteers (3 men, 7 women; age 34.6 ± 4.2 years) to evaluate the effect of duodenal acidification on the duodenogastric reflex, mucosal barrier function and immune activation
Perfusion with an acid solution resulted in activation of a duodenogastric reflex resulting in a relaxation of the proximal stomach, demonstrated by a decreased intragastric pressure (IGP) compared with saline perfusion (AUC: − 52.4 ± 13.2 vs. 9.6 ± 8.1 mmHg; P = 0.003) (Fig. 1A,B)
Summary
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. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. These acid mediated effects occur independently from mast cell activation. We hypothesized that impaired barrier function allows increased transepithelial passage of luminal substances triggering an immune response, which in turn can activate sensory neurons causing symptoms or alter duodenogastric reflex p athways[6]. Exogenous duodenal acid perfusion affects gastric sensorimotor function through duodenogastric reflex pathways in healthy volunteers, resulting in delayed gastric emptying, impaired gastric accommodation and hypersensitivity to gastric distension[12,13,14,15,16]. Whether an increased duodenal acid exposure can explain the observed increased duodenal permeability and low-grade inflammation in humans with FD, has not been studied
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