A Multi-Functional Prebiotic Strategy: Crosslinked 2′-Fucosyllactose-Potato Protein Hydrolysate Conjugates Encapsulating Resveratrol for Co-Delivery to Beneficial Gut Bacteria

Prebiotics are predominantly indigestible carbohydrate-based substrates selectively-utilized by beneficial gut-microbes to support host-health. We previously developed protein-containing prebiotics that co-deliver carbohydrate and protein substrates to the colon, where gut-microbes compete for the limited nitrogen availability, thereby enhancing microbial growth, metabolic activity, and host health compared with conventional carbohydrate prebiotics. Resveratrol is a grape-derived polyphenol with antioxidant, anti-inflammatory, and emerging prebiotic activity. Here, we developed a multifunctional protein-containing prebiotic system based on Maillard conjugates of 2′-fucosyllactose–potato protein hydrolysate (2′-FL-PPH) micelles encapsulating resveratrol, followed by genipin crosslinking. This crosslinked 2′-FL-PPH-resveratrol system is designed to limit premature protein and resveratrol absorption, enhancing their colonic co-delivery. We characterized the encapsulation efficacy, physicochemical properties, digestibility and colonic delivery. The conjugates (10 mg/mL 2′-FL-PPH) effectively entrapped resveratrol (600 µM), exhibiting an average particle size of ~28 nm and an encapsulation efficiency of 79.5 ± 4.9%. Binding studies demonstrated predominantly hydrophobic interactions between resveratrol and 2′-FL-PPH. The conjugates prevented resveratrol crystallization in aqueous media, while genipin crosslinking enhanced resistance to simulated gastrointestinal digestion and inhibited premature resveratrol release, increasing the fraction expected to reach the colon. Collectively, this system enables colonic co-delivery of carbohydrate, peptides, and resveratrol, providing a novel strategy for promoting beneficial-microbiota and gut-health.