Introduction

Confocal laser endomicroscopy (CLE) can detect acute duodenal epithelial disruption in response to food application, potentially identifying personalized elimination diets (1). A pilot study in functional dyspepsia (FD) showed that the 6-food elimination diet (6FED) provided symptom relief. (2). Earlier research in FD, however, showed that the high rate of acute food-induced mucosal alterations on CLE were not associated with altered permeability or changes in mast cell activation ex vivo (3).

Aims & Methods

To evaluate a personalized elimination diet in patients living with FD based on results of CLE, assessing duodenal mucosal changes to locally applied food solutions from the 6FED.
A randomized, double-blind, cross-over, sham-controlled trial was conducted in 17 Rome IV FD patients, in whom immunoglobulin E (IgE) sensitization to nutrients was excluded via food-specific serum IgEs. Baseline symptoms were assessed using the Leuven Postprandial Distress Scale (LPDS) and Patient Assessment of GI Disorders–Symptom Severity Index (PAGI-SYM). Index upper GI endoscopy (EGD) was followed at least 2 weeks later by an EGD with CLE. During CLE, duodenal mucosa was visualized at baseline and after consecutive, random administration of egg white, soy, milk, wheat, lyophilized fish/shellfish and nuts solutions. In case of a reaction to the first 2 food solutions, an additional CLE was scheduled. All patients underwent a crossover dietary intervention excluding foods to which they tested positively (real diet, RD) and negatively (sham diet, SD) in random order. Following 4 weeks of diet, LPDS and PAGI-SYM scores were reevaluated. Missing data were considered non-responder, based on an extreme case approach. Data are reported as mean ± SEM. Comparisons were done using a paired t-test or related-Samples Wilcoxon test, as applicable. Response rate was evaluated using a McNemar test. P<.05 is considered significant.

Results

Dietary outcome was available from 17 patients (age 35±3.7y, 16 female, BMI 22±0.7 kg/m2). In 7% of exams (n=2), acute alterations were already present at baseline. Twelve patients (71%) underwent a second CLE procedure. One patient dropped out after the first diet (which was RD). Three patients did not have a reliable RD/SD comparison due to non-response (n=1) or early response on CLE (n=2), underwent a standardized control diet, and were excluded from the analysis. Among the 14 patients in the cross-over dietary intervention, the proportion with a clinically significant 0.7 decrease in LPDS was similar for both diets (RD 4/14 vs. SD 2/14, p=0.41). No significant differences were found in LPDS subdomains or in the total PAGI-SYM score or PAGI-SYM fullness domain between the two diets (all p>.05).

Conclusion

In patients with FD, without systemic IgE-sensitization, CLE visualized a high rate of acute, food-induced, mucosal alterations, which could not be translated in symptom benefit following a dietary intervention excluding these foods vs. foods that did not trigger a reaction in this double-blind, controlled diet intervention study. None of the analyzed clinical outcome measures differed between the two diets. Given the results of this first double-blind controlled diet intervention in patients living with FD, CLE-based diets cannot be recommended in this population.

References

1. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Rocken C, Brasch J, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147(5):1012-20 e4.
2. Schol J, Vanuytsel T, Routhiaux K, Huang I, Balsiger L, Van Den Houte K, et al. The six-food elimination diet improves symptoms of functional dyspepsia. Submitted for publication. 2025.
3. Van de Bruaene C, Schol J, Balsiger L, Raymenants K, Toth J, Farre R, et al., editors. Observation of local, food-induced changes of the duodenal mucosa in functional dyspepsia cannot be translated in permeability alterations or changes in mast cell activation ex vivo. F; 2024; Bangkok, Thailand: Neurogastroenterology And Motility.

Introduction

Advances in non-celiac wheat sensitivity (NCWS) have proved that it should be considered a protean condition in which several potential triggers [e.g. gluten, wheat amylase-trypsin inhibitors, etc.] might determine an intestinal mucosal damage with increased permeability and exposure of foods/microbial peptides to immune cells (1,2), resulting in both a local and systemic inflammatory activation responsible for its gastrointestinal and extraintestinal manifestations (3,4). Up to 75% of NCWS subjects complain of multiple foods hypersensitivities (MFH) (5). These patients usually have clinical, immunological and histological features similar to wheat allergy patients, although without positive gluten/wheat IgE assays, allowing to hypothesize the existence of a non-IgE mediated hypersensitivity. In addition, several studies have reported an association between atopic diseases and NCWS.

Aims & Methods

This study aimed to define the presence and features of atopic diseases and other hypersensitivities (primarily food allergies/intolerances) in NCWS compared with celiac disease (CD) and irritable bowel syndrome/functional dyspepsia (IBS/FD) and to analyze a possible correlation between these diseases and NCWS clinical manifestations. This retrospective, multicenter study included NCWS patients diagnosed by double-blind placebo-controlled challenge with wheat. Their clinical, laboratory and histology data at diagnosis (i.e. before the start of a wheat-free diet) were analyzed and compared to control subjects with CD and IBS/FD. Specific allergology data, other than clinical/laboratory features typical of NCWS, were collected and analyzed: family and personal history of atopic diseases, type of allergens responsible, positivity of skin prick tests (SPT), patch tests and total and food-specific IgE.

Results

Atopic disease prevalence was higher in NCWS (32.8%) than in CD (19.3%) and IBS/FD (21.5%) (P=.001 for both). Similarly, NCWS subjects had a higher frequency of MFH (39.8%) and self-reported milk intolerance (SRMI) (65.9%) compared to the controls (P <.001 for both). Allergic asthma, either alone (P=.03) or associated with allergic rhinitis (P=.005), was more prevalent in NCWS compared to IBS/FD, which was more often associated with allergic conjunctivitis (P=.004) or allergic rhinitis alone (P=.02). Graminaceae hypersensitivity and nickel allergic contact dermatitis (Ni-ACD) were more frequent in patients with NCWS (70.1% and 17.8%) vs both CD (48.7% and 9.4%, P=.03 and P=.01, respectively) and IBS/FD (50.8% and 6.7%, P=.01 and P<.001, respectively). On multiple logistic regression analysis, a coexistent atopic disease (OR 1.481), MFH (OR 3.882) and SRMI (OR 2.259) were associated with the NCWS diagnosis. NCWS subjects with atopy compared to those without more frequently had Ni-ACD (P<.001) and SRMI (P=.03), positive patch test (P<.001), SPT for foods (P=0.001) and both total and food-specific serum IgE (P=.02 and P=.002, respectively). On multiple logistic regression analysis, positivity to patch test (OR 2.955), SPT for foods (OR 5.799), and food-specific serum IgE (OR 3.101) were confirmed as differentiating the 2 subgroups.

Conclusion

NCWS subjects have a higher frequency of atopic disease, MFH and SRMI compared to both CD and IBS/FD ones. These conditions could be expression of an underlying hypersensitivity milieu characterizing NCWS and might be of support in the differential diagnosis between NCWS and functional gastrointestinal disorders, if inserted into a broader diagnostic panel.

References

1) Zevallos VF, Raker V, Tenzer S, Jimenez-Calvente C, Ashfaq-Khan M, Rüssel N, et al. Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells. Gastroenterology. 2017;152:1100-1113.e12.
2) Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;65:1930–7.
3) Volta U, De Giorgio R, Caio G, Uhde M, Manfredini R, Alaedini A. Nonceliac Wheat Sensitivity. Gastroenterol Clin North Am. 2019;48:165–82.
4) Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria. Nutrients. 2015;7:4966–77.
5) Carroccio A, Mansueto P, Iacono G, Soresi M, D’Alcamo A, Cavataio F, et al. Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity. American Journal of Gastroenterology. 2012;107:1898–906.

Disclosure

This study is funded by the European Union - Next Generation EU, Mission 4, Component 1 CUP B53D23031860001, Project Code: P2022Z9RZY_001.

Introduction

Eosinophilic Esophagitis (EoE) is a clinicopathological disease that requires an integrated assessment combining clinical, endoscopic, and histological findings. Despite this, treatment decisions often remain symptom based. A treat-to-target strategy has recently been proposed to guide EoE management.

Aims & Methods

Retrospective single-center study of EoE patients followed between March 2012 and January 2024, with ≥12 months of follow-up. Clinical, endoscopic, histological data, and complications were assessed using the I-SEE score.

Results

A total of 82 patients with EoE were evaluated [75.6% (n=62) male, mean age 29 ± 13 years], with 37.8% (n=31) diagnosed during childhood. The most frequent symptom was food impaction (74.4%), and atypical symptoms were more common in pediatric patients (p=0.014). At baseline, 55.1% (n=43) presented with a fibrostenotic phenotype, more frequently in adults (p=0.012), and 32.9% (n=27) had moderate-to-severe disease based on the I-SEE score.
During follow-up, 56.1% (n=46) developed complications, most commonly food impaction requiring endoscopy. The presence of a fibrostenotic phenotype on initial endoscopy was a predictor of complications (OR 3.122; 95% CI 1.210–8.055; p=0.019). Both fibrostenotic phenotype (p=0.018) and moderate-to-severe I-SEE scores (p=0.004) were associated with increased need for therapeutic switching.
At 12 months, 50.0% (n=41) were asymptomatic; however, only 12.2% (n=10) had endoscopic healing and 9.8% (n=8) histologic remission. Throughout the study period, the rates of endoscopic and histologic healing remained below 25%.

Conclusion

The authors highlight the clinical dissociation of inflammatory activity and emphasize the importance of endoscopic and histologic healing to prevent disease progression.

References

Dellon, Evan S., et al. "A clinical severity index for eosinophilic esophagitis: development, consensus, and future directions." Journal of Allergy and Clinical Immunology 150.1 (2022): 33-47.