An <i>Enterococcus faecalis</i> isolate harboring both aerobic and anaerobic uric acid metabolic pathways alleviates hyperuricemia in mice

Probiotics have been demonstrated to be effective and safe for hyperuricemia (HUA) and gout treatment. Hence, identifying microbes with high uric acid- or purine-metabolizing ability is highly important. Due to the high load of uric acid in chicken feces, we hypothesized that the chicken gut would be an excellent source for new uric acid or purine-metabolizing microbes. In this study, we examined chicken gut contents to isolate an <i>Enterococcus faecalis</i> strain (designated CML390) that displayed high uric acid-degrading ability. <i>In vitro</i> experiments indicated that <i>E. faecalis</i> CML390 could effectively metabolize uric acid under both aerobic and anaerobic conditions, and the richer the nutrients, the higher the rate of uric acid degradation. By integrating genomics, transcriptomics, and metabolomics analyses, we revealed two pathways involved in aerobic and anaerobic uric acid degradation, respectively, in this isolate. <i>E. faecalis</i> CML390 relies on oxygen to metabolize uric acid into substances such as allantoin under aerobic conditions, while it also harbors a conserved uric acid-inducible gene cluster for anaerobic uric acid metabolism. An <i>in vivo</i> experiment showed that gavage with live <i>E. faecalis</i> CML390 in a mouse model of HUA (established using a combination of uric acid and potassium oxonate) significantly reduced serum uric acid levels and alleviated HUA. Our findings contribute to the exploration of the pathways and mechanisms of uric acid metabolism in intestinal microorganisms and provide a candidate probiotic for the treatment of HUA and gout.