Astilbin ameliorates hyperuricemia-associated renal injury in geese with gut-linked kynurenic acid immunometabolic remodeling.

Hyperuricemia (HUA) is increasingly recognized as a systemic inflammatory-metabolic disorder that contributes to immune-associated renal injury. Kynurenic acid (KYNA), a tryptophan-derived metabolite with reported immunomodulatory properties, has emerged as a potential mediator linking gut metabolism and distal organ inflammation. In this study, we investigated the protective effects of astilbin (ASB) against HUA and hyperuricemia-associated renal injury using an adenine-induced goose model, which is translationally relevant because geese naturally lack functional uricase, together with monosodium urate (MSU)-challenged primary renal tubular epithelial cells. By integrating multi-omics analyses, molecular docking, and molecular biology approaches, we found that ASB reduced serum uric acid, improved renal function, and attenuated inflammatory and fibrotic changes in vivo. ASB also suppressed circulating pro-inflammatory cytokines, restored intestinal barrier-related markers, and partially corrected gut microbial dysbiosis. Untargeted metabolomics revealed that KYNA was markedly reduced under HUA conditions and was restored by ASB treatment in both intestinal contents and serum. In parallel, ASB increased IDO2 expression in intestinal and hepatic tissues. In vitro, both ASB and KYNA attenuated MSU-induced inflammatory responses, restored urate transporter expression, and suppressed TGF-β/Smad-associated profibrotic signaling in primary renal cells. Collectively, these findings support a working model in which ASB ameliorates hyperuricemia-associated sterile inflammation and renal injury partly in association with gut-linked KYNA immunometabolic remodeling, accompanied by increased IDO2 expression. Because IDO1, kynurenine, KAT activity, and receptor/pathway inhibition were not assessed, the proposed mechanism should be regarded as hypothesis-supporting rather than definitively proven.