Integrated Epithelial Models Reveal Anti-Inflammatory and Barrier Modulatory Properties of Ozoile in Inflammatory Bowel Disease

Abstract Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition, with therapy-resistant patients undergoing surgery and a high risk of developing colorectal cancer. Novel therapeutic approaches have shown limited efficacy in IBD treatment, highlighting the need for safer and more personalized strategies. The potential of natural compounds to modulate inflammation suggests their use as a potential adjunct therapy for IBD patients. Methods: Intestinal epithelial cells organoids (IECOs) were derived from IBD and non-IBD tissues from IBD patients, and levels of inflammation markers and epithelial barrier permeability were assayed using qRT-PCR, WB, IF and leaking assays in the presence of Ozoile, an extra virgin olive oil enriched in ozonides. The Luciferase-based IBD-like organoid platform was generated for preliminary screening of anti-inflammatory drugs. Results: In this study, we showed that IBD-ECOs recapitulate tissue architecture and pathological state. We showed that Ozoile has anti-inflammatory and epithelial barrier modulatory effects and that the Luciferase IBD-like organoid model is sensitive to anti-inflammatory compounds. Conclusions: Using IECOs, the specific anti-inflammatory and regenerative properties of Ozoile were assessed. Notably, our study highlights the potential of an IBD-like organoid platform to use in high-throughput screenings for rapid selection of anti-inflammatory drugs.