Multistage oral astaxanthin targeted delivery system: Increasing serotonin levels with a dual therapeutic effect for alleviating inflammatory bowel disease and psychiatric disorders.

Inflammatory bowel disease (IBD) is associated with a notably high prevalence of psychiatric disorders. Since oxidative stress is an important feature of intestinal inflammation, astaxanthin (AXT), an effective and highly safe antioxidant, shows high therapeutic potential. Nonetheless, the utilization of AXT is hampered by its limited solubility and susceptibility. In this study, a multistage system (ALM@AG) was developed for enhancing the bioavailability and the targeted delivery of AXT. Moreover, ALM@AG was capable of targeting to the location of colon lesions by administering drugs, which was beneficial for effective treatments of colitis. The results showed that ALM@AG demonstrated high effectiveness in reducing inflammation, modulating gut microbiota, repairing intestinal barrier, and restoring metabolic homeostasis. Remarkably, ALM@AG exhibited a significant effect on treating depression-like behaviors suffering from colitis by regulating neurotransmitters and relieving brain inflammation. Notably, this study deeply explored interactions among genes, microbiota, and metabolites in the progression of IBD accompanied by psychiatric disorders, which may propose novel perspectives for investigating the gut-brain axis.