Enterococcus faecalis ameliorates hyperuricemia and maintains the epithelium barrier in a hyperuricemia mouse model

Abstract Background Hyperuricemia (HUA) is a major risk factor of gout and many other metabolic syndromes and shows a rapidly increasing incidence worldwide. Previous found that the gut microbiota and intestinal tract play important roles in the pathogenesis of HUA. However, most studies only revealed the association of gut microbiota and HUA without exploring the mechanistic causality, it remains unclear which gut microbiota play crucial roles in HUA. Results In the present study, we aimed to investigate key members of the gut microbiota in HUA and validate their effects on uric acid (UA) regulation. To this end, we deleted parts of the gut microbiota with antibiotics (NC-Ab group) and found that the abundance of Enterococcususwas significantly increased and the serum UA was significantly higher in antibiotic-fed mice (NC-Ab group) than no-antibiotic-fed mice (NC group). Subsequently, E. faecalis, the most important enterococcal species, was isolated and applied to HUA model mice for 2 weeks. We found E. faecalissupplementation could effectively alleviate HUA. Additional mechanistic investigation discovered that E. faecalis treatment could decrease the generation of UA and increase the excretion of UA through inhibition of xanthine oxidase (XO) activity and upregulating the expression of urate transporters (Abcg2, Glut9). Additionally, oral gavage with E. faecalis resulted in improvements in inflammation, restoration of impaired gut barrier, and amelioration of hepatic and renal function. Conclusions Our study demonstrated that E. faecalis plays a key role in regulating the UA balance and maintaining the intestinal barrier. E. faecalis could decrease UA level and protect gut barrier through inhibiting XO activity and increasing intestinal excretion. These findings may hold promise for developing intervention strategies for HUA.