Chinese bayberry exosome-like nanoparticles attenuate DSS-induced colitis via immunomodulation, barrier restoration, and microbiota remodeling.

Inflammatory bowel disease (IBD) is a chronic intestinal disorder characterized by intestinal barrier dysfunction and immune dysregulation, with limited safe and effective therapeutic options available. Owing to their biocompatibility and bioactivity, plant exosome-like nanoparticles (PELNs) have emerged as promising natural nanotherapeutics. In this study, exosome-like nanovesicles from Chinese bayberry (Myrica rubra) were isolated, characterized, and termed BELNs to investigate their therapeutic potential against IBD. Purified BELNs exhibited a typical bilayer membrane structure with a 100-300 nm size. Lipidomic, proteomic, and miRNA sequencing analyses revealed that BELNs contain bioactive components, including diacylglycerols, sphingomyelin, specific proteins, miRNAs, and polyphenols like cyanidin-3-O-glucoside. In vitro experiments demonstrated that BELNs were internalized by RAW 264.7 macrophages via galactose-mediated endocytosis, reducing LPS-induced proinflammatory cytokines (TNF-α and IL-1β) and increasing anti-inflammatory IL-10. In vivo, orally administered BELNs accumulated predominantly in the murine gastrointestinal tract. In a DSS-induced IBD model, BELNs alleviated disease symptoms, preserved intestinal tissue integrity, and enhanced barrier function by upregulating tight junction protein ZO-1 and mucin MUC2. Additionally, BELNs remodeled the gut microbiota by decreasing Escherichia-Shigella and enriching beneficial short-chain fatty acid-producing bacteria. These findings highlight BELNs' potential as safe and effective nanotherapeutics for treating ulcerative colitis through immunoregulation, barrier repair, and microbiota modulation.