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ACUTE MUCOSAL REACTIONS FOLLOWING FOOD ADMINISTRATION IN IRRITABLE BOWEL SYNDROME ARE NOT ASSOCIATED WITH ALTERED PERMEABILITY OR MAST CELL ACTIVATION EX VIVO

Date
May 20, 2024

Introduction: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction characterized by abdominal pain associated with bowel movements. Local allergic reactions have been implicated as a mechanism underlying the food-related symptoms often reported by IBS patients. Confocal laser endomicroscopy (CLE) has shown acute disruption of the duodenal epithelium in IBS after food administration, which has been linked to IBS symptom generation.
Aim: Assess the acute effects of food on the duodenal mucosa of IBS patients and whether visualized changes are associated with altered permeability, secretion or markers of mast cell activation ex-vivo.
Methods: In non-constipated Rome IV IBS patients, allergic sensitization to nutrients was excluded by specific serum IgE tests. Index upper GI endoscopy (EGD) was followed by CLE performed during a second EGD. Duodenal mucosa was visualized at baseline and after sequential administration of lyophilized fish, nuts, egg white, soy, milk, and wheat solutions through the working channel in randomized order. Serum was obtained at baseline and 30 minutes after visualization of acute mucosal alterations. Biopsies were obtained at index EGD and after acute alterations to measure transepithelial electrical resistance (TEER) and potential differences in Ussing chambers and tryptase levels in biopsy supernatants following 24h incubation. Data are reported as mean ± SEM. Comparisons were done using two-sided t.tests in Rstudio. P-value < 0.05 is considered significant.
Results: 34 CLE exams were carried out in 20 patients (age 34±2 y, 90%f, BMI 23 ± 1 kg/m2).
While acute alterations were visualized at baseline in 9% of exams (n=3), 91% (n=31) presented alterations only after food exposure. The highest percentage of acute alterations was observed after administration of milk (8 altered / 14 exposed); the distribution of reactions per food is presented in table 1. There was no difference in serum tryptase after acute alterations compared to baseline (3.96μg/L vs. 4.04μg/L, p=0.3). TEER did not change after an acute reaction compared to baseline (25Ωxcm2 vs 27Ωxcm2, p=0.3), nor did the potential difference as a marker of secretion (- 1.17mV vs. -1.8mV, p=0.9). Tryptase content in biopsy supernatants was not altered after an acute reaction compared to baseline (1.03µg/g vs. 1.22µg/g, p=0.3). After acute reactions, changes in ex vivo tryptase release compared to baseline were not different among the food types (table 1).
Conclusion: In this group of non-constipated IBS patients, we found a high rate of acute food induced mucosal alterations as visualized with CLE. The visualized alterations were not linked to altered permeability or secretion ex vivo. After acute alterations, systemic tryptase remained unchanged as did tryptase release from biopsy supernatants.
<i>Figure 1: Ex vivo measurements at baseline and after visualization of acute mucosal alterations. Panel A: Transepithelial electrical resistance (TEER), Panel B: Tryptase release in biopsy supernatants after 24h incubation normalized to biopsy weight.</i>

Figure 1: Ex vivo measurements at baseline and after visualization of acute mucosal alterations. Panel A: Transepithelial electrical resistance (TEER), Panel B: Tryptase release in biopsy supernatants after 24h incubation normalized to biopsy weight.

<i>Table 1: Number of exams with exposure to respective nutrients (baseline visualization was done in all exams), number of visualized alterations and percentage of acute alterations. Change in tryptase release in biopsy supernatants after acute alterations upon exposure to the respective nutrient compared to baseline (no significant differences, one-way ANOVA)</i>

Table 1: Number of exams with exposure to respective nutrients (baseline visualization was done in all exams), number of visualized alterations and percentage of acute alterations. Change in tryptase release in biopsy supernatants after acute alterations upon exposure to the respective nutrient compared to baseline (no significant differences, one-way ANOVA)


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