Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Recent studies have linked gut microbiota to gout, but the role of microbiota in ameliorating HUA remains unclear. This study established a novel HUA model in geese and investigated how Lactobacillus rhamnosus GG (LGG) alleviates HUA. Antibiotic and fecal microbiota transplantation (FMT) experiments were conducted, and the effects of LGG and its metabolites were evaluated in vivo and in vitro. Multi-omics analysis revealed that the Lactobacillus genus is associated with purine metabolism in HUA. The study showed that LGG and its metabolites alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis of LGG enzymes ABCT, iunH, and pbuX demonstrated nucleoside degradation functions. Multi-omics and correlation analysis in HUA patients and geese revealed that serum proline deficiency and changes in Collinsella and Lactobacillus may be associated with HUA. The findings suggest that a goose model of diet-induced HUA is promising, and LGG and proline could be potential therapies for HUA. HUA is a global metabolic disease with increasing prevalence. The prevalence is particularly high in coastal areas, such as the USA, Japan, and European countries. In China, the number of HUA patients increased by 30% between 1998 and 2018. HUA is a major risk factor for gout, chronic kidney disease, type 2 diabetes, and cardiovascular disease. The serum uric acid (UA) level is greatly influenced by diet, such as high-purine diets, fructose, and alcohol. Humans and poultry lack uricase, making them vulnerable to HUA. Mouse models have been used for HUA studies, but they face challenges in modeling. Geese are highly susceptible to gout, and gout in goslings has high morbidity and mortality. The mechanism of HUA in geese is similar to that in humans. Excessive protein consumption is strongly associated with diet-induced HUA and gout in these species. Strategies to modulate gut microbiota have been studied for diseases like HUA, obesity, and metabolic syndrome. Emerging evidence shows that gut microbiota dysbiosis is linked to abnormal urate degradation and systemic inflammation in HUA and gout. Metagenomic analyses revealed that Enterobacteriaceae contribute to UA reduction in healthy individuals. Bacteroides species are abundant in HUA patients. The gut microbiota in HUA plays a role in nucleotide and amino acid metabolism, making intestinal microbes a potential target for treating HUA and gout. Recent research shows that some gut microbes participate in UA degradation. For example, Limosilactobacillus fermentum and LactiplantibHyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Recent studies have linked gut microbiota to gout, but the role of microbiota in ameliorating HUA remains unclear. This study established a novel HUA model in geese and investigated how Lactobacillus rhamnosus GG (LGG) alleviates HUA. Antibiotic and fecal microbiota transplantation (FMT) experiments were conducted, and the effects of LGG and its metabolites were evaluated in vivo and in vitro. Multi-omics analysis revealed that the Lactobacillus genus is associated with purine metabolism in HUA. The study showed that LGG and its metabolites alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis of LGG enzymes ABCT, iunH, and pbuX demonstrated nucleoside degradation functions. Multi-omics and correlation analysis in HUA patients and geese revealed that serum proline deficiency and changes in Collinsella and Lactobacillus may be associated with HUA. The findings suggest that a goose model of diet-induced HUA is promising, and LGG and proline could be potential therapies for HUA. HUA is a global metabolic disease with increasing prevalence. The prevalence is particularly high in coastal areas, such as the USA, Japan, and European countries. In China, the number of HUA patients increased by 30% between 1998 and 2018. HUA is a major risk factor for gout, chronic kidney disease, type 2 diabetes, and cardiovascular disease. The serum uric acid (UA) level is greatly influenced by diet, such as high-purine diets, fructose, and alcohol. Humans and poultry lack uricase, making them vulnerable to HUA. Mouse models have been used for HUA studies, but they face challenges in modeling. Geese are highly susceptible to gout, and gout in goslings has high morbidity and mortality. The mechanism of HUA in geese is similar to that in humans. Excessive protein consumption is strongly associated with diet-induced HUA and gout in these species. Strategies to modulate gut microbiota have been studied for diseases like HUA, obesity, and metabolic syndrome. Emerging evidence shows that gut microbiota dysbiosis is linked to abnormal urate degradation and systemic inflammation in HUA and gout. Metagenomic analyses revealed that Enterobacteriaceae contribute to UA reduction in healthy individuals. Bacteroides species are abundant in HUA patients. The gut microbiota in HUA plays a role in nucleotide and amino acid metabolism, making intestinal microbes a potential target for treating HUA and gout. Recent research shows that some gut microbes participate in UA degradation. For example, Limosilactobacillus fermentum and Lactiplantib