Ulva lactuca Extracellular Vesicles Protect Against High-Fat Diet-Induced Intestinal Damage via Nrf2/Keap1/HO-1 Activation

High-fat diets (HFDs) impair the intestinal barrier by increasing permeability and oxidative stress, which contributes to obesity-related disorders. Ulva lactuca, a marine green alga, produces extracellular vesicles (UEVs) that remain underexplored as functional food components. In this study, UEVs were isolated and characterized, showing a cup-like shape morphology with average diameter of 188.8 nm. Functional assays demonstrated that UEV treatment attenuated oxidative stress, reduced apoptosis, and restored tight junction proteins. In a gut-on-a-chip model, UEVs improved transepithelial electrical resistance (TEER) and enhanced mucin secretion under HFD-mimicking stress. Mechanistic studies revealed that UEVs activated the Nrf2/Keap1/HO-1 signaling pathway, promoting nuclear translocation of Nrf2 and upregulation of antioxidant genes. Collectively, these findings highlight UEVs as novel food-derived nanostructures with dual functions in oxidative stress reduction and intestinal barrier protection, supporting their potential in functional food applications targeting metabolic gut disorders.