Zhiyang Du

Gastrointestinal barriers (acidic environment, mucus barrier, tight junctions, and microbiota metabolism) have long constrained the oral bioavailability of food-derived bioactives, especially lipophilic constituents. Recent advances in functionalized nanoparticle strategies offer sophisticated techniques to address these challenges. Specifically, precise control of particle size, morphology and surface functionalization enhances mucus penetration and cellular uptake of nanocarriers. Advanced nanocarrier strategies, such as mucosal adhesion, receptor-mediated targeting, and co-delivery with permeation enhancers, facilitate efficient absorption by opening intercellular gaps and activating specific endocytosis pathways. Intelligent designs for pH, enzyme, redox, and microbiome responses resulted in precise protection and targeted release of cargoes in various gastrointestinal segments. This review summarizes critical strategies for absorption-optimized oral nanoplatforms, including absorption mechanisms, mucosal retention, receptor-mediated endocytosis, co-delivery with absorption enhancers, and multi-strategy coupling. We emphasize strategic orientations for maximizing oral absorption efficiency of bioactive ingredients, offering a transformative framework for architecting next-generation oral nanocarrier platforms of food-derived components.

Inflammatory bowel disease (IBD) is characterized by intestinal barrier dysfunction and bile acid (BA) dysmetabolism. BA metabolism was a pivotal regulator in the "gut-liver axis" to maintain intestinal homeostasis. Ovalbumin-derived peptides (OVA-Ps) exhibit potential in barrier repair; however, their systemic mechanisms within the microbiota-BA-host network remain underexplored. This study investigates the therapeutic potential of the oligomer OVA-P in a DSS-induced colitis mouse model. OVA-P administration significantly alleviated colitis symptoms, restored colon length, reduced pro-inflammatory cytokines (tumor necrosis factor-α), and enhanced antioxidant markers (SOD). Mechanistically, the OVA-P reshaped gut microbiota composition, suppressed bile salt hydrolase (BSH), and elevated conjugated BAs (e.g., taurocholic acid) levels. These changes activated the farnesoid X receptor (FXR) pathway, upregulating tight junction protein (ZO-1), and mucin (MUC-2) expression, thereby restoring intestinal barrier integrity. Metabolomic and metagenomic analyses confirmed the OVA-P-mediated modulation of the gut-liver axis through FXR-SHP/FGF15 signaling, highlighting its role in maintaining BA homeostasis. These findings provide insights into the use of OVA-P as a dietary intervention for IBD by targeting microbiota-BA-FXR interactions, offering a foundation for high-value egg protein applications in functional foods.