Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

高尿酸血症（HUA）是嘌呤代谢异常引起的代谢综合征。尽管最近的研究已经注意到肠道微生物群与痛风之间的关系，但微生物群是否可以改善 HUA 相关的全身嘌呤代谢仍不清楚。在本研究中，我们构建了鹅的 HUA 新型模型，并研究了鼠李糖乳杆菌GG (LGG) 对 HUA 产生有益作用的机制。在该 HUA 鹅模型中使用了抗生素施用和粪便微生物移植 (FMT) 实验。在体内和体外评估了 LGG 及其代谢物对 HUA 的影响。LGG的异质表达和基因敲除揭示了LGG的作用机制。多组学分析表明，乳酸菌属与 HUA 中嘌呤代谢的变化有关。这项研究表明LGG及其代谢物可以通过肠-肝-肾轴缓解HUA。LGG酶ABC型多药转运系统（ABCT）、肌苷尿苷核苷N-核糖水解酶（iunH）和黄嘌呤通透酶（pbuX）的全基因组分析、异质表达和基因敲除证明了LGG中核苷降解的功能。对 HUA 患者和该鹅模型的多组学和相关性分析表明，血清脯氨酸缺乏以及柯林斯氏菌和乳酸菌的变化可能与 HUA 的发生有关。我们的研究结果证明了饮食诱导 HUA 的鹅模型的潜力，LGG 和脯氨酸可能是 HUA 的有前途的疗法。