## 1 Introduction
found that patients with functional gastrointestinal disorders, including IBS and functional dyspepsia, had a significantly higher prevalence of atopic conditions than controls [19]. Similarly, in a Japanese study involving over 8000 patients, a significant association was identified between allergic diseases and functional gastrointestinal disorders, including IBS, suggesting shared immune mechanisms [20]. These studies, however, face some limitations, including non-standardized diagnostic criteria, lack of blinding, and uncertainty regarding the clinical relevance of observed associations. Prolonged dietary restrictions can lead to nutritional deficiencies, necessitating careful medical and nutritional supervision. In this contest, an integrated and personalized approach with dietitians and nutritionists can help with and prevent IBS, also improving quality of life. Furthermore, IgG-based tests seem to be controversial as they do not necessarily indicate a pathological response but may reflect a normal immune response to food exposure [21; 22; 23]. This lack of specificity limits their diagnostic utility and may lead to overdiagnosis or misdiagnosis [24]. Diagnostic criteria lack standardization, with laboratories using variable methods and reference ranges, reducing result comparability across settings. Furthermore, many tests for food intolerance lack scientific validation, making it difficult to assess their true clinical efficacy [25]. Exclusion diets based on such tests also face some challenges. While some studies report symptom improvement with exclusion diets, methodological limitations such as short study duration and unrepresentative participant selection, cast doubts on the generalizability of findings. Perceived efficacy may partly result from placebo or nocebo effects rather than true clinical benefits [26]. However, recent findings suggest that maybe personalized IgG-guided diets may provide symptom relief, particularly in IBS-C and IBS-M patients [27]. Recently, the focus has shifted toward understanding local rather than systemic alterations, particularly within the intestinal mucosa, offering new perspectives on food reactions and immunological interactions in IBS. There are currently no studies in the literature about the application of confocal laser endomicroscopy (CLE) for the most known non-IgE food allergy, Food Protein-Induced Enterocolitis Syndrome (FPEIS). Confocal laser endomicroscopy (CLE) is an advanced and innovative diagnostic endoscopic imaging technology that provides real-time, high-resolution cellular-level visualization of the gastrointestinal epithelium [28; 29; 30; 31]. Two main CLE systems have been marketed: endoscope-based CLE (eCLE), integrating the confocal microscope into the endoscope, and probe-based CLE (pCLE), using miniaturized confocal probes inserted through standard endoscopic accessory channels. pCLE is the only used technique currently (Figure 1). This technique uses a low-power laser to illuminate tissue and collects reflected fluorescent light through a confocal optical system, ensuring high spatial resolution and real-time histological imaging [29; 32]. Using intravenous contrast agents (such as fluorescein), visualization of cellular and subcellular structures is enhanced, enabling the detection of mucosal alterations with high sensitivity and specificity [28]. The high temporal resolution of CLE enables the recognition of dynamic changes in the mucosa [33]. CLE has been utilized in the evaluation and diagnosis of neoplasms, chronic inflammatory conditions (e.g., IBD),  
Figure 1: Characteristics of intestinal tissue findings: arrows indicate histological aspect (above) and confocal laser endomicroscopy (below) with the possible dynamic changes (normal, fluorescence leakage, and cell shedding) after the food antigen provocation test. and both malignant and benign diseases of the pancreas and bile ducts [30; 34; 35]. It allows \"optical biopsies\", reducing random sampling and enhancing diagnostic accuracy [34].