A multi-omics strategy for the identification of novel biomarkers predicting treatment response in patients with inflammatory bowel disease

Background: The therapeutic armamentarium for inflammatory bowel disease (IBD) is expanding, and the need for biomarkers able to predict treatment response and support personalized therapeutic strategies has therefore increased. This study aimed to identify early biomarkers of response to infliximab through a multi-omics approach including circulating micro-RNA (miRNA) profiling and serum metabolomics. Methods: Patients with moderately-to-severely active ulcerative colitis (UC) and Crohn’s disease (CD) starting on infliximab were prospectively enrolled within the Florence IBD Biobank. For miRNA profiling, we included UC patients only, whereas the metabolomics analysis included both UC and CD patients, together with matched non-IBD controls. Plasmatic miRNAs were assessed at baseline and after treatment induction using the Nanostring Human v3 miRNA Assay. Serum metabolomic profiling was performed by 1H NMR spectroscopy. MiRNA and metabolomic signatures were analyzed in relation to 12-month clinical and endoscopic outcomes. Results: The miRNA study included 12 UC patients, equally distributed between remitters (achieving combined clinical and endoscopic remission after 12 months) and non-remitters. Distinct miRNA signatures emerged at baseline and after induction, with miR-200a-3p after induction showing the strongest predictive performance. Functional analyses linked these miRNAs to immune regulation, epithelial integrity, and TGF-β/epithelial–mesenchymal transition signaling. The metabolomics study included 34 IBD patients and 34 matched non-IBD controls. At baseline, IBD patients showed a metabolic profile characterized by higher lactate and lower glucose levels, together with alterations in amino acid, lipid, ketone body, and tricarboxylic acid cycle metabolism, consistent with a Warburg-like inflammatory phenotype. Reductions in trimethylamine-N-oxide and increases in creatine and pyruvate after treatment induction were associated with better endoscopic outcomes. Conclusions: This pilot study shows that circulating miRNAs and serum metabolites capture complementary biological dimensions of infliximab response in IBD. Integrating multi-omics profiling with clinical aspects may therefore represent a promising approach to improve patient stratification and selection while advancing precision medicine strategies. Larger prospective studies are needed to validate these findings.