Non-Invasive Multimarker Strategy Combining IL-17A, Neutrophil–Albumin Ratio, and Fecal Calprotectin for Accurate Discrimination of IBD from IBS-D

Differentiating inflammatory bowel disease (IBD) from diarrhea-predominant irritable bowel syndrome (IBS-D) remains a major clinical challenge due to overlapping symptoms and the limited specificity of single biomarkers. A reliable, non-invasive multimarker approach is needed to improve diagnostic accuracy and reduce unnecessary endoscopic procedures. To evaluate the diagnostic performance of serum interleukin-17A (IL-17A), neutrophil-to-albumin ratio (NAR), and fecal calprotectin (FCP), individually and in combination, for discriminating IBD from IBS-D and healthy controls in Egyptian patients. In this case–control study, 300 participants (100 with IBD, 100 with IBS-D, and 100 healthy controls) were enrolled. Serum IL-17A, NAR, and FCP were measured, and subgroup analysis was performed for infected and non-infected IBS-D patients. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, with optimal cutoffs determined by the Youden index. A combined biomarker model was constructed using logistic regression. All biomarkers demonstrated a significant stepwise increase from healthy controls to IBS-D and IBD (p < 0.001). IL-17A, NAR, and FCP were elevated in IBS-D compared with controls, indicating low-grade inflammation, but were highest in IBD. No significant differences were observed between infected and non-infected IBS-D patients. Among individual markers, NAR showed the highest diagnostic accuracy (AUC = 0.923), followed by FCP (AUC = 0.884) and IL-17A (AUC = 0.859). The combined model significantly improved performance (AUC = 0.973), achieving 89% sensitivity and 96% specificity. IBS-D is associated with measurable systemic and intestinal inflammation independent of infection status. The combined biomarker model integrating IL-17A, neutrophil–albumin ratio, and fecal calprotectin demonstrated promising discriminatory performance for differentiating IBD from IBS-D. These findings suggest the potential applicability of combined non-invasive biomarkers in future diagnostic stratification approaches. However, the model was developed and evaluated within a single cohort, and external validation in independent populations is required before future potential clinical application. A multimarker diagnostic panel integrating IL-17A, neutrophil–albumin ratio, and fecal calprotectin demonstrated promising diagnostic performance for differentiating inflammatory bowel disease from IBS-D. The combined model may contribute to future diagnostic stratification strategies in patients with chronic diarrhea. However, these findings were derived from a single cohort and require validation in independent populations before broader clinical application.