Diagnostics of Fecal Calprotectin Across Gastrointestinal Diagnoses With Presence of Infection

Background Distinguishing inflammatory bowel disease (IBD) from post-infectious or functional gastrointestinal symptoms remains challenging. Fecal calprotectin (FC) is widely used to differentiate inflammatory from non-inflammatory disease, yet real-world performance in the context of infectious comorbidity and indeterminate presentations remains incompletely characterized. Methods A prospective cross-sectional analysis of 702 adults undergoing FC testing within a tertiary-care gastroenterology (GI) network (September–December 2024) was performed to evaluate the influence of recent infection on FC interpretation and diagnostic classification. Classifications included IBD, irritable bowel syndrome (IBS), microscopic colitis, and indeterminate. FC distributions were compared using Kruskal–Wallis testing with Dunn’s correction. Diagnostic performance for identifying IBD was assessed at standard thresholds (≥ 50, 150, 250, and 500 µg/g) with infection stratification. Results Patient stratification by FC resulted in 39.7% confirmed IBD, 16.9% IBS, 41.6% Indeterminate, and 1.7% microscopic colitis. Graded FC values followed: IBS < Microscopic < Indeterminate < IBD; p < 0.001). Median FC was lowest in IBS (19.6 µg/g) and highest in IBD (219 µg/g). Infection was documented in 55% of patients and was associated with modest FC elevation across diagnoses. Diagnostic specificity improved with increasing FC thresholds, rising from 35.7% at ≥ 50 µg/g to 88.7% at ≥ 500 µg/g. Infection reduced specificity at lower thresholds, with greatest interpretive uncertainty from 50–250 µg/g. Conclusion FC remains a valuable biomarker for distinguishing inflammatory from non-inflammatory disease alongside simultaneous infectious consideration. Borderline FC elevations require cautious interpretation in post-infectious settings, with repeat testing after infection resolution.