Gut-kidney axis modulation by viable and inactivated <i>Akkermansia muciniphila</i> mitigates avian hyperuricemia through microbial-metabolic crosstalk

Hyperuricemia (HUA) has become the fourth most important health-threatening risk factor after hypertension, hyperglycemia, and hyperlipidemia, but the efficacy of existing uric acid-lowering treatments (ULT) is poor, and there is an urgent need to explore novel ULT strategies. <i>Akkermansia muciniphila</i> (<i>A. muciniphila</i>), a next-generation probiotic, shows promise in promoting intestinal homeostasis and metabolic regulation. Previous studies have demonstrated the potential application of <i>A. muciniphila</i> in ULT, but its specific mechanism has not been elucidated. In this study, we isolated a strain of <i>A. muciniphila</i>, named K101, from the cecum of goslings. <i>In vitro</i> experiments showed that K101 directly degrades uric acid, suggesting a potential microbial-metabolic crosstalk mechanism for anti-HUA. <i>In vivo</i> experiments showed that K101 increased the abundance of uric acid metabolism-related microbiota, such as <i>A. muciniphila</i> and <i>Lactobacillus</i>. Functionally, K101 synergistically promoted uric acid excretion by activating the intestinal excretory protein ABCG2 and inhibiting the renal uric acid reabsorption protein GLUT9. In addition, K101 provides a stable environment for uric acid metabolism by inhibiting renal inflammatory responses. Overall, <i>A. muciniphila</i> K101 exerts anti-HUA effects by remodeling the intestinal microbiota and excretion of uric acid through the gut-renal axis. This study offers new insights into microbial-metabolic crosstalk in uric acid metabolism in <i>A. muciniphila</i> and identifies potential targets for gout prevention and ULT strategy development.IMPORTANCEThe rising prevalence of hyperuricemia (HUA) underscores the need for new therapies and treatment approaches. Our study highlights the developmental and therapeutic potential of natural uric acid-degrading bacteria discovered in the avian gut, expanding the range of bacteria with possible medical applications. Another key finding is the notable efficacy of microbiota metabolites in alleviating HUA. While the underlying mechanisms warrant further investigation, these findings offer promising insights into microbiota-based therapeutics.