• Gut microbiota-derived exosome-like nanoparticles mediate gut-brain communication in POCD after CRC surgery.
• These nanoparticles induce autophagy-dependent ferroptosis in hippocampal neurons, linking microbial dysbiosis to cognitive decline.
• Key ferroptosis markers (ATG5, COX2, GPX4, FTH1) are altered, offering potential biomarkers for POCD.
• Findings suggest novel therapeutic targets for CRC-associated POCD via modulation of gut microbiota or exosome signaling.