Lentinula edodes-derived exosome-like nanoparticles improve curcumin stability and biotransformation via gut microbiota interactions.

Exosome-like nanoparticles (ELNs) from edible sources are emerging as natural carriers for stabilizing bioactive compounds. This study investigated Lentinula edodes-derived ELNs (LeELNs) as a delivery system for curcumin. LeELNs efficiently encapsulated curcumin (69.25 %) into stable vesicles <200 nm and significantly improved its stability during simulated gastrointestinal digestion. In vivo, Le-Cur exhibited prolonged intestinal retention and elevated levels of hydrogenated metabolites in the small intestine, liver, and plasma compared with free curcumin. To elucidate this enhancement, PKH26-labeling combined with flow cytometry and 16S rRNA sequencing revealed preferential uptake of LeELNs by beneficial taxa such as Bacteroidaceae and Lactobacillaceae. Consistently, in vitro fermentation with human microbiota showed strengthened microbial biotransformation of curcumin into bioactive tetrahydro- and hexahydrocurcumin while promoting beneficial bacterial growth. Overall, LeELNs protect curcumin, extend its intestinal residence, and enhance microbiota-driven metabolism, highlighting the potential of fungus-derived vesicles as natural delivery systems.