The Uric Acid Degrading Probiotics MC1 in Quercetin Nanocoatings and Bioactive Polysaccharides Microgels for Anti‐Hyperuricemia and Gut Microenvironment Modulation

ABSTRACT Hyperuricemia (HUA), a metabolic disorder associated with inflammatory and gut microbiota dysbiosis, demands effective intestinal‐targeted therapies. Herein, a novel intestinal‐targeted delivery system was designed based on quercetin nanorods coated Lactobacillus paracasei MC1 encapsulated within manganese‐crosslinked Mesona chinensis polysaccharide microgels (MCPM‐QUE‐MC1). The MC1 strain, isolated from the traditional fermented food “Jiangshui”, exhibits potent uric acid‐degrading activity. The quercetin nanocoating enhances mucosal adhesion and antioxidative capacity through a prebiotic nanointerface, while manganese ions impart nanozyme‐like catalytic activity, scavenging hydrogen peroxide (H 2 O 2 ) and modulating the intestinal microenvironment. This synergistic assembly protects probiotics from gastric acidity and promotes intestinal colonization, as validated in mouse and pig models. In HUA mice, oral administration of MCPM‐QUE‐MC1 significantly reduced serum uric acid levels to 101.83 ± 6.88 µmol L −1 , increased MC1 abundance by 8.37‐fold, improved renal function, suppressed inflammatory cytokines, and restored gut microbial homeostasis by notably enriching short‐chain fatty acid‐producing bacteria. Mechanistically, the therapeutic effect arises from enhanced uric acid degradation, inhibition of hepatic xanthine oxidase, reduction of intestinal permeability, and systemic endotoxemia. Overall, this study establishes a promising probiotic‐polyphenol prebiotic‐microgel composite platform for HUA alleviation, offering a new insight into gut microbiota‐targeted therapies for metabolic diseases.