Anti-hyperuricemia effects of a polysaccharide-protein complex from Lentinula edodes mediated by gut-kidney axis

In order to investigate the effects of Lentinula edodes (L. edodes) on hyperuricemia, a polysaccharide-protein complex (LEPP) was prepared and characterized, and the activity was also systematically studied. LEPP was mainly composed of proteins (18.55 %) and polysaccharides (36.98 %) with three polysaccharide fractions (molecular weights were 8.98 x 10(6), 7.34 x 10(7) and 1.15 x 10(7) g/mol). The experiment results showed that 250-1000 mg/kg/day LEPP could decrease the serum uric acid (UA) level from 281.62 to 109.42-138.12 mu mol/L (p < 0.001), and there were significant differences between high and low doses (p < 0.05). LEPP simultaneously improved renal function, relieved oxidative stress and inflammation in the kidney and regulated renal UA transporters (URAT1, GLUT9, OAT1 and ABCG2) of hyperuricemia rats. Furthermore, gut microbiota dysbiosis and intestinal barrier function disruption were modified by LEPP. Among them, LEPP could reverse the relative abundances of Parabacteroides, Lachnospiraceae, Colidextribacter, UCG-010, Monoglobus, Lactobacillus and Muribaculaceae, which were associated with regulating the UA level, renal function and the expression of renal UA transporters in hyperuricemia rats through correlation analysis. Conclusively, LEPP prevented the pathological process of hyperuricemia through regulating the gut-kidney axis, which provided its complementary role in existing anti-hyperuricemia treatment strategies.