Microalgae‐Based Hydrogel for Inflammatory Bowel Disease and Its Associated Anxiety and Depression

Abstract Patients diagnosed with inflammatory bowel disease (IBD) exhibit a notable prevalence of psychiatric disorders, such as anxiety and depression. Nevertheless, the etiology of psychiatric disorders associated with IBD remains uncertain, and an efficacious treatment approach has yet to be established. Herein, an oral hydrogel strategy (SP@Rh‐gel) is proposed for co‐delivery of Spirulina platensis and rhein to treat IBD and IBD‐associated anxiety and depression by modulating the microbiota‐gut‐brain axis. SP@Rh‐gel improves the solubility, release characteristics and intestinal retention capacity of the drug, leading to a significant improvement in the oral therapeutic efficacy. Oral administration of SP@Rh‐gel can reduce intestinal inflammation and rebalance the disrupted intestinal microbial community. Furthermore, SP@Rh‐gel maintains intestinal barrier integrity and reduces the release of pro‐inflammatory factors and their entry into the hippocampus through the blood‐brain barrier, thereby inhibiting neuroinflammation and maintaining neuroplasticity. SP@Rh‐gel significantly alleviates the colitis symptoms, as well as anxiety‐ and depression‐like behaviors, in a chronic colitis mouse model. This study demonstrates the significant involvement of the microbiota‐gut‐brain axis in the development of IBD with psychiatric disorders and proposes a safe, simple, and highly efficient therapeutic approach for managing IBD and comorbid psychiatric disorders.