Lysozyme-induced 3D assembly of quercetin-zinc rod-like nanocolloids and its functional impact on antioxidant, gut microbiota, and lipid metabolism.

Quercetin exhibits antioxidant, anti-inflammatory, and lipid metabolism-regulating activities, but poor aqueous stability limits its functional application. Here, quercetin-Zn2+-lysozyme nanorod colloids (QZLs) were constructed as a ternary assembly system to balance quercetin structural stability with gastrointestinal functional accessibility and enhance its microbiota-modulating potential during colonic fermentation. Quercetin coordinated with Zn2+ to form QZ nanorods, followed by lysozyme-mediated hierarchical three-dimensional assembly through electrostatic attraction, hydrophobic interactions, and possible Zn2+-amino acid residue coordination. QZLs improved quercetin storage stability in aqueous systems, retaining more than 95% ABTS radical-scavenging capacity after 20 days. In vitro colonic fermentation showed that QZLs reshaped gut microbiota, enriched beneficial taxa including Mediterraneibacter and Bifidobacterium, and promoted SCFAs production. QZL-20 (lysozyme concentration of 20 μg/mL) reduced lipid droplet accumulation and TG levels and downregulated PLIN2 expression. This lipid-lowering effect may be associated with stabilized quercetin delivery and increased SCFAs. These findings indicate that Zn2+-mediated coordination and lysozyme-assisted assembly enhance quercetin stability, microbiota modulation, and lipid-lowering potential.