Biomolecular Fingerprint of Crohn's Disease: A Comparative Raman Spectroscopic Study of Blood and Tissue Samples

Crohn's disease (CD) is typically diagnosed through endoscopy and histological analysis of biopsies. Currently, specific noninvasive biomarkers for accurate diagnosis and monitoring of CD remain unavailable. This study investigates Raman spectroscopy (RS) as a noninvasive diagnostic and monitoring tool for CD. Plasma and biopsy samples from 66 participants (55-CD, 11-controls) were analyzed to identify disease-specific molecular alterations. RS revealed significant spectral differences (p < 0.05) in amino acids, proteins, carbohydrates, and carotenoids. Decreased valine and arginine levels were consistent with mucosal damage and inflammation, supported by reduced carbohydrate signals indicating barrier impairment. Carotenoid depletion reflected oxidative stress-related inflammation. Correlations between plasma and tissue spectra suggested that plasma RS can reflect local tissue inflammation. Despite the small and heterogeneous cohort, RS detected biochemical shifts toward healthy profiles following biologic therapy. These findings support RS as a minimally invasive approach for detecting inflammation-associated molecular alterations, holding potential to guide personalized disease management.