Next-generation prebiotics: Maillard-conjugates of 2′-fucosyllactose and lactoferrin hydrolysates beneficially modulate gut microbiome composition and health promoting activity in a murine model

Current prebiotics are predominantly carbohydrates. However, great competition exists among gut microbes for the scarce protein in the colon, as most consumed protein is digested and absorbed in the small intestine. Herein we evaluated in-vivo novel next-generation prebiotics: protein-containing-prebiotics, for selectively-targeted delivery of protein to colonic probiotics, to boost their growth. This system is based on micellar-particles, composed of Maillard-glycoconjugates of 2′-Fucosyllactose (2′-FL, human-milk-oligosaccharide) shell, engulfing lactoferrin peptic-then-tryptic hydrolysate (LFH) core. This core–shell structure lowers protein-core digestibility, while the prebiotic glycans are hypothesized to serve as molecular-recognition ligands for selectively targeting probiotics. To study the efficacy of this novel prebiotic, we fed C57BL/6JRccHsd mice with either 2′-FL-LFH Maillard-glycoconjugates, unconjugated components (control), or saline (blank). Administration of 2′-FL-LFH significantly increased the levels of short-chain-fatty-acids (SCFAs)-producing bacterial families (Ruminococcaceae, Lachnospiraceae) and genus (Odoribacter) and the production of the health-related metabolites, SCFAs, compared to the unconjugated components and to saline. The SCFAs-producing genus Prevotella significantly increased upon 2′-FL-LFH consumption, compared to only moderate increase in the unconjugated components. Interestingly, the plasma-levels of inflammation-inducing lipopolysaccharides (LPS), which indicate increased gut-permeability, were significantly lower in the 2′-FL-LFH group compared to the unconjugated-components and the saline groups. We found that Maillard-glycoconjugates of 2′-FL-LFH can serve as novel protein-containing prebiotics, beneficially modulating gut microbial composition and its metabolic activity, thereby contributing to host health more effectively than the conventional carbohydrate-only prebiotics.