From waste to wellness: pomelo peel derived exosome-like nanoparticles reshape gut microbiota and enhance beneficial metabolites.

Pomelo processing by-products, traditionally regarded as agricultural waste, are underutilized bioactive-rich candidate feedstocks for circular economy. This study optimized isolation protocol (differential centrifugation with PEG precipitation) for Pomelo Peel Exosome-Like Nanoparticles (PPELNs), uniform nanovesicles (195.8 ± 78.6 nm) with gastrointestinal stability. Proteomic analysis identified 1145 proteins enriched in carbohydrate, energy, amino-acid metabolism and stimulus response. In vitro human fecal fermentation model demonstrated PPELNs intervention altered gut microbiota, increased beneficial taxa (Bifidobacterium, Blautia, Phascolarctobacterium) and suppressed Escherichia-Shigella, suggesting potential prebiotic effects. Metabolomic profiling revealed elevated bioactive compounds (naringenin 7-rhamnoglucoside, auraptenol). PPELNs fermentation enhances short-chain fatty acids (SCFAs), including acetic, propionic, butanoic and valeric. Further analysis showed microbiota-metabolite correlations. Propionic, butyric and auraptenol positively correlated with Blautia but negatively with Escherichia-Shigella; naringenin 7-rhamnoglucoside positively correlated with Phascolarctobacterium and Ruminococcus. These findings upcycle pomelo peel into a high-value functional ingredient, provide the first evidence establishing specific metabolite-microbe correlations.