INTEGRATING PATIENT-DERIVED ORGANOIDS AND NATURAL COMPOUNDS FOR DIAGNOSTIC AND THERAPEUTIC INNOVATION IN IBD

Inflammatory Bowel Disease (IBD), including Crohn’s disease and ulcerative colitis, presents a major clinical challenge due to its chronic nature and the limitations of existing therapies. In this context, patient-derived organoids (PDOs) have emerged as powerful preclinical models that preserve the cellular complexity, architecture, and molecular features of the original intestinal tissues, making them ideal tools for both disease modeling and drug screening.

In this study, we established intestinal PDOs from both healthy individuals and IBD patients, demonstrating their ability to recapitulate key features of the native tissue, including the expression of lineage-specific markers and pro-inflammatory mediators. Notably, the IBD-derived organoids retained elevated levels of IL-8 and CLDN1, reflecting their inflammatory state and validating them as a faithful in vitro model of the disease.

Leveraging this platform, we investigated the anti-inflammatory potential of an ozonated extra virgin olive oil derivative, using a luciferase reporter system driven by NF-κB response elements. Upon TNFα-induced inflammation, this natural compound significantly reduced the NF-κB activation in both 2D cell lines and 3D organoid systems, showing comparable efficacy to that of standard anti-inflammatory compounds such as dexamethasone. These findings were further supported by immunofluorescence, which revealed decreased nuclear translocation of p65 following treatment.

Importantly, this compound displayed minimal cytotoxicity at effective concentrations in preliminary viability assays.

Overall, this study underscores the critical value of PDOs in faithfully modeling IBD and evaluating novel therapeutic agents. Our results highlight an olive oil derivative as a promising natural compound with strong anti-inflammatory effects and pave the way for PDO-based personalized medicine approaches in chronic intestinal inflammation. This organoid-driven strategy offers a robust and translational platform for screening natural products and developing safer, more targeted treatments for IBD.