## 3 Results
### Mucosal Alterations and Food Allergy in IBS: Insights from Confocal Laser Endomicroscopy

Table 1: Diagnostic accuracy of confocal laser endomicroscopy findings (barrier dysfunction in the terminal ileum and in the colon). \begin{table}
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In recent years, the field of microendoscopy has provided new insights into microscopic alterations in the intestinal mucosa, even in IBS patients [37]. Real-time imaging with CLE has been employed to evaluate duodenal mucosal changes following acute food exposure in a pioneering study [38]. Baseline imaging of the mucosa is performed, and then food components are introduced via the endoscope's working channel to observe changes linked to altered mucosal permeability. Normally, fluorescein is absent in the lumen due to an intact mucosa, but acute food reactions cause fluorescein extravasation and luminal particles (\"cell shedding\"), appearing as dark spots against the illuminated lumen. [PERSON] and colleagues analyzed a pattern of mucosal changes via CLE, suggesting that these may represent non-classical forms of food allergy due to localized immune reactions in patients with negative IgE serological tests [38]. In their study, 22 out of 36 IBS patients (61.1%) showed positive responses to food challenges administered in liquid or standardized suspension forms (CLE+), while no reactions were observed in 14 CLE- IBS patients and 10 healthy controls. Specifically, there was an increase in the number of intraepithelial lymphocytes (IELs) from an average of 18.7 \(\pm\) 0.9 to 24.7 \(\pm\) 1.4 IELs/field (_p_ = 0.0001), increase in epithelial breaks from 5.5 \(\pm\) 0.6 to 11.9 \(\pm\) 1.5 per 1000 epithelial cells (_p_ < 0.001), and significant widening of intervillous spaces from 8.1 \(\pm\) 3.5 \(\upmu\)m to 41.1 \(\pm\) 2.5 \(\upmu\)m (_p_ = 0.0001). Subsequently, CLE+ patients followed an exclusion diet based on the food antigen provocation test results. After four weeks, 19 out of 22 CLE-positive patients reported a greater than 50% reduction in symptoms (abdominal pain, bloating, diarrhea, or constipation). At 12 months, the average symptom reduction reached 74%, with some patients achieving complete remission. The same group further explored mucosal reactions to food challenges in 155 IBS patients and 10 healthy controls [39]. Duodenal biopsies, as well as molecular and histological analyses, were also conducted to investigate changes in tight junctions and inflammatory responses. CLE+ patients underwent an exclusion diet based on the food identified during challenges. Among IBS participants, 70% of IBS participants exhibited immediate reactions to food components (CLE+), with 60.5% reacting to wheat. Patients who excluded reactive foods showed significant long-term symptom improvements (up to 6 months of follow-up). Additionally, the authors reported increased claudin-2 expression and reduced occludin levels in the duodenal mucosa of CLE+ patients. Tryptase levels in duodenal fluid showed no differences between CLE+ and CLE- patients or HCs and remained unchanged after antigen exposure. Duodenal fluid eosinophilic cationic protein (ECP) levels were significantly higher in CLE+ patients compared to healthy controls, with a post-stimulation average of 29.4 \(\pm\) 51.2 mg/L in CLE+ versus 6.5 \(\pm\) 7.9 mg/L in controls (_p_ = 0.03). Compared to CLE- patients, ECP levels were higher but did not reach statistical significance (CLE-: 15.5 \(\pm\) 19 mg/L) [39]. [PERSON] and colleagues conducted a study comparing a selective diet based on CLE results with a more restrictive diet excluding five major allergens (milk, eggs, wheat, soy, and yeast) [43]. The 172 IBS participants, who had non-IgE-mediated food intolerances and positive CLE results, received support via a digital app providing personalized guidelines, recipes, and tools to monitor adherence and symptoms. Primary endpoints included improvements in quality of life (FAQLQ-AF) and reductions in gastrointestinal symptom severity (IBS-SSS).