The Role of Fecal Biomarkers in Monitoring Crohn’s Disease: Innovations in Diagnosis and Management

Crohn’s disease (CD) requires continuous assessment of inflammatory activity to support treat-to-target strategies and prevent progressive bowel damage. Although endoscopy remains the reference standard, its invasive nature limits repeated use, emphasizing the need for reliable non-invasive biomarkers. This narrative review summarizes current evidence on established and emerging fecal biomarkers for CD monitoring and discusses their biological relevance, diagnostic and prognostic performance, and potential role in predicting treatment response. Relevant evidence on fecal calprotectin, lactoferrin, myeloperoxidase, lipocalin-2, S100A12, high-mobility group box-1, plasminogen activator inhibitor-1, fecal microRNAs, and lipidomic signatures was critically evaluated. Fecal calprotectin remains the most established biomarker, although variability in cut-off values, reduced sensitivity in isolated ileal disease, and limited specificity restrict its performance in certain clinical settings. Emerging biomarkers show promising complementary value, but most require further validation and assay standardization before routine implementation. Multimarker strategies integrating fecal biomarkers with clinical assessment, blood biomarkers, imaging, and endoscopy may provide a more comprehensive evaluation of disease activity. Future integration of multi-omics approaches could further support individualized monitoring and therapeutic decision-making in CD.