Food-based modulation of intestinal urate handling in the context of systemic purine metabolism: An integrated framework linking purine bioaccessibility, epithelial transport, microbial catabolism, and barrier resilience

Approximately one-third of human urate disposal occurs through the intestine, where dietary purine release, epithelial transport, microbial catabolism, and barrier homeostasis jointly shape systemic urate balance. Existing reviews usually address these processes separately, which limits their translation into functional-food design. This review proposes the Four-Node Intestinal Urate Regulation (FIUR) framework, comprising three operational nodes and one cross-cutting node. Node 1 covers preabsorptive purine control and is resolved into luminal purine release and bioaccessibility (Node 1A), a lumen-side process independent of epithelial integrity, and CNT2-mediated nucleoside uptake (Node 1B); Node 2 covers epithelial urate efflux through ABCG2 and its partner carriers SLC52A1, GLUT9, and SLC17A4; Node 3 covers microbial interception of dietary purines and luminal urate degradation; and Node 4 represents barrier integrity and ecological resilience. Host xanthine oxidoreductase-dependent urate production and renal handling are defined as interacting background rather than framework nodes, and food effects on these routes, exemplified by the dose-dependent dual action of fructose, are mapped at the framework boundary. The framework distinguishes direct food effects from microbiota- and inflammation-dependent constraints, including butyrate- and hippurate-mediated support of ABCG2 and inflammation-associated impairment of transporter localization. Food-derived components are classified by chemical class and graded by evidence type and experimental model, separating human-validated findings from rodent-only evidence that is further qualified by interspecies differences in uricase activity and intestinal transporter repertoire. This framework supports evidence-aware, multi-node design of functional foods for hyperuricemia management.