Abstract
Background: Coix seed oil (YRO), rich in unsaturated fatty acids, has emerged as a promising intervention for hyperuricemia (HUA) due to its potential to alleviate oxidative damage and support organ health. Methods: The fatty acid composition of YRO was determined by gas chromatography-mass spectrometry (GC-MS). A HUA mouse model was established, and serum markers and hepatic enzymes were evaluated. Renal mitochondrial function was assessed using immunohistochemistry and immunofluorescence, and urate transporter expression, along with key signaling proteins, was quantified by Western blot analysis. Additionally, gut microbiota composition was analyzed, and non-targeted metabolomics was performed to observe alterations in serum lipid metabolites. Results: YRO significantly reduced serum uric acid (UA) levels and normalized hepatic enzyme activities. Histological evaluation revealed less tissue damage in both the kidney and the intestine. In the kidney, YRO improved mitochondrial function and supported antioxidant defenses via regulation of Keap1/Nrf2 signaling. In the intestine, YRO enhanced barrier integrity by increasing ZO-1, Occludin, and Claudin-1 expression. Moreover, YRO modulated gut microbiota by increasing beneficial bacteria (Muribaculaceae, Prevotellaceae UCG-001, Lachnospiraceae_ NK4A136_group, Akkermansia) while suppressing harmful species (Bacteroides, Dubosiella). Lipid metabolomics indicated a restoration of phospholipid balance through modulation of the PI3K/AKT/mTOR pathway. Conclusions: YRO supported metabolic health by promoting UA homeostasis, enhancing mitochondrial function, reinforcing antioxidant capacity, and maintaining gut integrity. These findings suggest that coix seed oil could serve as a nutritional supplement in managing HUA and related metabolic disturbances.