Bilirubin Nanomedicine Restores Destructed Intestinal Barrier and Mucosal Immunity in Colitis. undefined

Inflammatory bowel disease (IBD) manifests in the destructed intestinal barrier, dysregulated mucosal immunity, and gut microbiome homeostasis. However, conventional anti-inflammatory medications for IBD therapy partially alleviate symptoms but are unable to restore the destructed barrier and dysregulated immune. Here, we report a nanomedicine comprising bilirubin-conjugated low molecular weight water-soluble chitosan-bilirubin (LMWC-BRNPs) that enables restoration of the intestinal barrier, mucosal immunity, and gut microbiome, thereby exerting robust therapeutic efficacy. In a mouse model of dextran sulfate sodium salt (DSS)-induced colitis, due to the mucoadhesiveness of LMWC, orally administered LMWC-BRNPs could retain in the GI tract much longer than the other non-mucoadhesive BRNPs. LMWC-BRNPs treatments led to the considerable recovery of the destructed intestinal barrier compared to the current IBD medication, 5-aminosalicylic acid (5-ASA). Orally administered LMWC-BRNPs were taken up by pro-inflammatory macrophages and inhibited their activity. Simultaneously they increased the population of regulatory T cells, thereby leading to the recovery of dysregulated mucosal immunity. Gut microbiome analysis revealed that LMWC-BRNPs treatments significantly attenuated the increase of an inflammation-related microorganism called Turicibacter, resulting in the protection of gut microbiome homeostasis. Taken together, LMWC-BRNPs could restore the normal functions of the intestine and have a high potential to be used as nanomedicine for IBD therapy.