Renoprotective effects of perennial ryegrass attenuate UA mediated renal damage via modulating gut microbiota and anti-oxidative defense

Hyperuricemia (HUA) is a metabolic disorder and a major cause of gout in geese, commonly exacerbated by concentrate diets rich in protein and calcium. Elevated uric acid (UA), a potent pro-oxidant, contributes to renal injury and is strongly influenced by dietary composition and gut microbiota. Therefore, research for natural feed ingredients that can regulate UA homeostasis and oxidative stress is particularly essential. Perennial ryegrass, a fiber-rich forage containing abundant minerals and antioxidant flavonoids, may mitigate these adverse effects, however its renoprotective potential in goslings remains unclear. This study investigated the protective effects of perennial ryegrass against UA-induced oxidative stress and renal damage in goslings. High-through 16S rRNA and LC-MS metabolomics were performed to determine the effect of ryegrass on the gut microbiota-metabolite axis in goslings. Biochemical indexes, histopathology, immunofluorescence, gene expressions, and western blotting were used to observe the renoprotective potential of ryegrass. Ryegrass significantly lowered serum UA and creatinine levels (p < 0.05) by upregulating renal UA-excreting transporters (ABCG2, OAT1 and OAT3) and downregulating UA-reabsorbing transporters (URAT1 and GLUT9). Histopathology and microbial profiling revealed that ryegrass reduced tubular damage, fibrosis, and immune cell infiltration, accompanied by enrichment of short chain fatty acid-producing bacterial taxa. Transcriptional, protein, and immunofluorescence analysis demonstrated that ryegrass suppressed inflammatory cytokines (IL-1β, IL-18, TNF-α) through inhibition of the NLRP3/caspase-1/Keap1 axis, likely related to decreased renal UA burden. In parallel, it strengthened antioxidant defenses by upregulating Nrf2, which increased GSH-Px, CAT, and SOD activities and lowered MDA and ROS accumulation. Metabolomics further demonstrated higher levels of antioxidant metabolites (caffeic acid, kaempferol, skimmin, quercetin, and ferulic acid) in ryegrass-fed goslings relative to the concentrate-fed group. These findings highlight the renoprotective potential of perennial ryegrass in alleviating UA-induced oxidative renal injury and provide new insights into its value as a functional forage in the geese industry.