Dietary Oligosaccharides Isolated from Coix Seed Mitigate Hyperuricemia through Modulation of Lipid Metabolites and Intestinal Homeostasis

Hyperuricemia (HUA) is a prevalent metabolic disorder associated with chronic disease, posing significant global health challenges. Coix seed, a traditional cereal, has shown therapeutic potential against HUA, with oligosaccharides serving as its primary active components. However, the mechanisms of Coix seed oligosaccharides in HUA management remain underexplored. In this study, a novel oligosaccharide was isolated from Coix seed (CSO) through enzymatic hydrolysis and column chromatography. Structural analysis revealed that the CSO is primarily composed of glucose, with a backbone of →4)-β-Glc<i>p</i>-(1→ linkages. CSO exhibited significant hypouricemic effects in both adenosine-induced HK-2 cells and HUA mice by inhibiting XOD activity and regulating urate transporter expression. Furthermore, CSO restored lipid imbalances, particularly in PS and PC, and modulated gut microbiota by increasing <i>Ruminococcus</i>, <i>Akkermansia</i>, and <i>Lachnospiraceae</i> abundance to alleviate HUA-related systemic disturbances. Importantly, CSO alleviated HUA-induced renal injury by downregulating the IL-6/JAK2/STAT3 signaling pathway. This study provided meaningful evidence supporting the effect of CSO on HUA and offered new directions for natural oligosaccharide interventions in metabolic health.