Fecal calprotectin and other biomarkers are not prospectively associated with food protein-induced allergic proctocolitis

Objectives: Diagnosis of food protein-induced allergic proctocolitis (FPIAP) is challenging due to the lack of noninvasive biomarkers. We evaluated fecal calprotectin, eosinophil-derived neurotoxin (EDN), and zonulin as potential biomarkers for diagnosing FPIAP, while also examining normal ranges in healthy infants under 12 months. Methods: We analyzed 214 stool samples from 115 infants (63 with clinically diagnosed FPIAP) over the first year of life from a large prospective observational cohort. We examined the range for each biomarker in infants over time and compared biomarker concentrations in infants with and without FPIAP using linear mixed-effects modeling. We also compared biomarker concentrations to existing 16S rRNA microbiome profiles using MaAsLin2. Results: Concentrations of calprotectin, EDN, and zonulin were not associated with FPIAP at the time of diagnosis (p = 0.81, p = 0.74, p = 0.24, nor longitudinally (p = 0.356, p = 0.0791, p = 0.333). Calprotectin was found to decrease significantly over the first 12 months of life for both groups (p < 0.001), while EDN and zonulin did not significantly change (p = 0.903, p = 0.043). There was no associated dysbiosis or microbial signature with any of the three biomarkers. Conclusion: Concentrations of calprotectin, EDN, and zonulin were not associated with clinically diagnosed FPIAP in our cohort. Very high levels of calprotectin are noted in early infancy in asymptomatic healthy infants, and we provide normal ranges across the first year of life for all three biomarkers. This study does not support the use of fecal calprotectin, EDN, or zonulin for diagnosis of FPIAP.