Understanding Colitis Progression and Treatment Response in Murine and Canine Models with Raman Metabolic Profiling...

Ulcerative colitis is a chronic inflammatory condition of the gastrointestinal tract with a rising global prevalence that underscores the urgent need for noninvasive approaches to monitor disease progression and treatment response. Recent evidence links metabolic alterations in colitis to disease severity, suggesting that metabolic profiling is a promising biomarker strategy. Here, we employed Raman spectroscopy (RS) as a sensitive, label-free approach to profiling serum and tissue metabolomes in murine and canine models of colitis. We identified 16 statistically significant metabolites in the murine sera that distinguished healthy from colitis mice with an area under the curve receiver operating characteristic (AUC-ROC) value of 0.98. Both serum and tissue metabolites showed moderate to strong correlations with proinflammatory cytokines, disease activity index, bodyweight, and histology scores of colon. This approach was extended to canine sera, differentiating colitic dogs treated with a synbiotic-IgY supplement from placebo controls with an AUC of 0.81, highlighting Raman features broadly associated with sugars and amino acids as key discriminative metabolites. Our analysis revealed that metabolic changes in placebo-treated dogs were diet-driven, whereas synbiotic supplementation modulated lipid and fatty acid profiles associated with the gut microbiota activity. Proteomic analysis validated RS findings and showed significant alterations in pathways associated with lipid transport and also demonstrated that synbiotic supplementation reduced inflammatory pathways while promoting extracellular matrix remodeling and gut healing. Collectively, these results indicate that metabolic profiling offers an impactful strategy for the diagnosis of UC and prediction of therapeutic response, laying the groundwork for personalized medicine in inflammatory diseases.