ROS-Responsive Curcumin Nanoparticles Reprogram the Gut-Brain Axis for Inflammatory Bowel Disease Therapy

Inflammatory bowel disease is not merely a localized inflammatory disorder of the colon, but also involves profound dysregulation of the intricate gut-brain axis. In this study, we developed reactive oxygen species (ROS)-responsive curcumin nanoparticles (CUR@ALG-Se) that precisely reprogram this neuro-immune-microbial axis to disrupt the cycle of inflammation. The smart delivery system protects curcumin from gastric degradation and enables targeted, ROS-triggered release specifically in the inflamed colonic tissue. Through this site-specific action, CUR@ALG-Se alleviates oxidative stress by scavenging excess ROS. The restored redox balance promotes the growth of beneficial bacteria while suppressing harmful species, leading to reestablished microbial homeostasis. Subsequently, the reconstituted microbiota enhances the production of short-chain fatty acids, which serve as the primary energy source for colonocytes and facilitate the repair of the intestinal barrier. This reinforced barrier acts as a protective wall, preventing the translocation of pro-inflammatory cytokines and bacterial endotoxins into the systemic circulation, thereby disrupting harmful gut–brain communication. Ultimately, this strategy successfully reduces hippocampal inflammation and ameliorates depression-like behaviors in mice, achieving integrated modulation of the gut–brain axis. The platform demonstrates broad potential for the treatment of other inflammatory and neurodegenerative disorders, offering promising avenues for the treatment of IBD and its neuropsychiatric comorbidities.