10-Hydroxy-2-decenoic Acid Attenuates Colitis-Associated Cognitive Dysfunction via IFITM3-Related Gut–Brain Axis Inflammation

10-Hydroxy-2-decenoic acid (10-HDA), a bioactive compound in royal jelly, has anti-inflammatory and antioxidant properties. This study investigates whether 10-HDA alleviates cognitive impairment caused by dextran sulfate sodium (DSS)-induced chronic colitis, focusing on IFITM3, an immune regulator linked to intestinal and neuroinflammation. DSS treatment increased IFITM3 in the colon and hippocampus, resulting in neuroinflammation and cognitive deficits. 10-HDA reduced colonic inflammation, suppressed IFITM3-mediated NF-κB activation, improved cognitive performance, and attenuated astrocyte reactivity. IFITM3 knockout mice showed less colitis and neuroinflammation, and 10-HDA's effects were diminished in these mice, suggesting an IFITM3-related mechanism. These results suggest 10-HDA as a potential dietary agent for gut-brain axis health in chronic inflammation.