Honeysuckle‐Derived Nanovesicles Regulate Gut Microbiota for the Treatment of Inflammatory Bowel Disease

Abstract Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease, significantly impairs patients’ quality of life and is characterized by a compromised intestinal barrier, pathogenic bacterial colonization, and chronic inflammation. The gut microbiota has emerged as a therapeutic target for IBD owing to its role in modulating immune responses, metabolic pathways, and barrier function. In this study, the therapeutic potential of honeysuckle‐derived nanovesicles (HNVs) in a dextran sodium sulfate‐induced murine model of UC is investigated. Oral administration of HNVs alleviates colitis symptoms, reduces colonic inflammation and histopathological damage, restores Treg/Th17 balance, and repairs intestinal barrier integrity. These effects are associated with favorable alterations in the gut microbiota, including an increase in beneficial bacteria and a decrease in pathogenic species, along with elevated levels of short‐chain fatty acids (SCFAs), which are essential for maintaining mucosal immunity and barrier function. Moreover, metabolomic analysis reveals that HNVs promoted bile acid (BA) absorption and regulated BA metabolism, contributing to the maintenance of intestinal immune homeostasis. Collectively, these findings demonstrate the protective effects of HNVs through modulation of SCFA levels and BA metabolism, supporting their potential as a promising therapeutic strategy for the treatment of IBD.