Abstract: Objective: To investigate the effect and underlying mechanism of live and pasteurized Akkermansia muciniphila on serum uric acid levels and inflammation in hyperuricemic mice. Methods: An Institute of Cancer Research (ICR) mouse model of hyperuricemia was established by oral administration with potassium oxonate and hypoxanthine combined with dietary supplementation with 20% of yeast extract for three weeks. The mice in the treatment groups were gavaged with live and pasteurized Akkermansia muciniphila, separately. Blood and tissue samples were collected to measure serum uric acid concentration as well as liver xanthine oxidase activity and to analyze renal and intestinal pathology by hematoxylin and eosin (HE) staining. Results: Both live and pasteurized Akkermansia muciniphila could reduce the concentration of serum uric acid in mice to a certain extent, and down-regulate the activity and protein expression of hepatic xanthine oxidase (XOD), thereby reducing the production of uric acid in the liver. Histopathological analysis showed that both the kidney and intestinal tract of mice in the model group were damaged, including glomerular atrophy, inflammatory cell infiltration in renal interstitium, and shortened intestinal villi. Treatment with Akkermansia muciniphila alleviated these symptoms. Akkermansia muciniphila intervention could also down-regulate Toll-like receptors 4 (TLR4) and Caspase-1 in the kidney and intestine, thereby inhibiting the expression of interleukin (IL-1β) and effectively alleviating the inflammatory responses in mice. This study shows that Akkermansia muciniphila can be used to improve hyperuricemia in mice, and pasteurized Akkermansia muciniphila also exhibits the same effect. These findings can lay a theoretical basis for developing probiotics and probiotic-related products for improving hyperuricemia in the future.

Key words: hyperuricemia;?Akkermansia?muciniphila; xanthine oxidase; inflammatory response