Grape Exosome–Like Nanovesicles Reverse the Prediabetic State in Mice

OBJECTIVE: This research explored the effect of grape exosome-like nanovesicles (GELNs) on reversing prediabetic conditions in mice and investigated the underlying mechanisms via metabolomic and gut microbiota analyses. METHODS: Twenty-four C57BL/6J mice were divided into four groups: normal control, prediabetic model, GELN intervention, and nutrient intervention. Prediabetic models were induced in all but the control group, and then the intervention groups were treated for 8 weeks. RESULTS: GELNs significantly improved fasting blood glucose, 2-h postprandial glucose, insulin levels, and total cholesterol. Metabolomic analysis found enriched differential metabolites, highlighting tryptophan and riboflavin metabolism. 16S rDNA sequencing showed no difference in α-diversity but differences in β-diversity. At the phylum level, the abundance of Firmicutes and Desulfobacterota was higher in the GELN group (Group W), while Bacteroidota and Proteobacteria were more abundant in the model group (Group T). At the genus level, Akkermansia was significantly reduced in the GELN group (Group W), indicating a notable shift in gut microbiota composition. CONCLUSION: GELNs may reverse prediabetes in mice by improving metabolic health and gut homeostasis, offering new insights for prediabetes prevention and treatment.