Integrated Immune–Gut Profiling Identifies an Exploratory Pediatric Inflammatory Intestinal Profile Associated with Food-Specific IgG Reactivity

The clinical relevance of food-specific IgG antibodies in pediatric gastrointestinal disorders remains controversial. Although current international guidelines discourage their use as standalone diagnostic tools, their significance within a broader immune–gut inflammatory framework has not been sufficiently explored. This study aimed to investigate associations between food-specific IgG reactivity, inflammatory and permeability biomarkers, microbiological findings, and abdominal ultrasound abnormalities in children with chronic gastrointestinal symptoms. Methods: (1) Children presenting chronic gastrointestinal symptoms associated with food-specific IgG polysensitization, elevated inflammatory and permeability biomarkers, and abdominal ultrasound abnormalities (number (n) = 196); (2) a symptomatic gastrointestinal group without the complete multimodal profile (n = 146); and (3) a control group with normal abdominal ultrasound findings and biomarkers within reference ranges (n = 210). All participants underwent food-specific IgG testing using a 216-antigen ELISA panel, abdominal ultrasound examination, and assessment of intestinal inflammatory and permeability biomarkers. Food-specific IgG antibodies were not interpreted as diagnostic markers of food allergy or food intolerance. Comparative analyses, correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Food-specific IgG polysensitization was significantly more frequent among children presenting the multimodal inflammatory profile compared with symptomatic and control groups (all p < 0.001). Reactivity predominantly involved gluten-containing cereals, dairy proteins, and mixed gluten–dairy patterns. Elevated fecal calprotectin, zonulin, and fecal histamine concentrations were more frequently observed in this subgroup, together with a higher prevalence of ultrasound abnormalities, including bowel wall thickening and mesenteric lymphadenopathy. Correlation analyses demonstrated significant associations between cumulative IgG burden and bowel wall thickness (r = 0.48, p < 0.001), while fecal calprotectin showed the strongest association with ultrasound abnormalities (r = 0.62, p < 0.0001). Multivariable logistic regression identified elevated calprotectin, increased zonulin, IgG polysensitization, and mixed gluten–dairy reactivity as independent predictors of pathological ultrasound findings. The integrated multimodal model demonstrated higher classification performance than isolated biomarkers. Conclusions: Children presenting chronic gastrointestinal symptoms, food-specific IgG polysensitization, inflammatory biomarker abnormalities, and ultrasound changes represented a multimodal clinical subgroup within the study population. These findings support evaluating food-specific IgG reactivity within a broader immune–gut assessment framework rather than as a standalone diagnostic biomarker. The observed associations should be considered exploratory and hypothesis-generating, requiring prospective validation and mechanistic investigation.