Bioinspired Nanozyme-Exoskeletonized Yeast-derived Polysaccharides for Treating Comorbid Anxiety and Depression in Inflammatory Bowel Disease_16s-seq
Inflammatory bowel disease (IBD) is a chronic condition frequently accompanied by psychological comorbidities, such as anxiety and depression. Although current treatments may alleviate some of these symptoms, the intricate pathogenesis of these comorbidities highlights an urgent need for the development of novel therapeutic strategies. Herein, we develop a series of nanozyme-exoskeletonized yeast-derived polysaccharides (NZEP) by integrating nanozymes with yeast-derived polysaccharides using an insect sclerotization-inspired strategy. Among them, NZEPTA-Ce, with the highest degree of nanozyme-exoskeletonization, is capable of disrupting the inflammatory vicious cycle by inhibiting MAPK and NF-kB-mediated inflammatory signaling pathways. Oral administration of NZEPTA-Ce in male mice enables effective retention and accumulation in inflamed colonic regions, reverses the homeostasis imbalance of intestinal inflammation and promoting intestinal barrier repair. Furthermore, NZEPTA-Ce treatment reverses gut microbiota dysbiosis and optimize the composition of microbial metabolites, thereby alleviating anxiety and depressive symptoms associated with IBD. This study provides a safe and promising therapeutic strategy for the management of IBD patients and their associated psychological comorbidities.