Study Of The Effects And Approaches Of Lactobacillus On Hyperuricaemia Alleviation

Hyperuricaemia is a disease characterized by an excessively increased serum urate concentration.In recent years,the incidence of hyperuricaemia is increasing and the current incidence of hyperuricaemia in China is as high as 13.3%.Lactobacillus has the potential to alleviate hyperuricaemia.Most studies have pointed out the hypothesis that purine degradation might be an important way for Lactobacillus to alleviate hyperuricaemia,but this hypothesis is suspicious because purines are mainly absorbed in the small intestine while the place where Lactobacillus plays a role is in the large intestine.Few studies supposed that Lactobacillus might inhibit the activity of xanthine oxidase(XOD)by regulating the gut microbiota.Based on background above,the study aimed to screen for Lactobacillus with the potential of relieving hyperuricaemia and investigate its anti-hyperuricaemia approaches using in vitro experiments and animal experiments.The main results are shown as follows.(1)Screening of Lactobacillus to alleviate hyperuricaemia.10 strains of Lactobacillus(5strains of Lactobacillus rhamnosus and 5 strains of Lactobacillus reuteri)were selected to administer to hyperuricaemia mice induced by potassium oxonate and hypoxanthine for 4weeks.The results showed that Lactobacillus rhamnosus CCFM1130,Lactobacillus rhamnosus CCFM1131 and Lactobacillus reuteri CCFM1132 significantly relieve hyperuricaemia symptoms of mice,as reflected by reduced uric acid concentrations in serum and urine,downregulated XOD activity in serum and liver,decreased lipopolysaccharide in serum and inflammation of liver,and improved the renal injury.(2)Exploring the relationship between hyperuricemia alleviation by Lactobacillus and its ability to degrade purines.The ability of Lactobacillus to reduce serum uric acid in vivo and the degradation of different purines(adenosine,guanosine,hypoxanthine)in vitro were combined to analyze.The results showed that all the 10 Lactobacillus had no degradation abilities on hypoxanthine and had significant inter-species differences in capacity of adenosine and guanosine degradation.The capacities in degrading adenosine and guanosine of Lactobacillus reuteri were much higher than that of Lactobacillus rhamnosus,but the alleviation of hyperuricaemia by Lactobacillus was not significantly related to their abilities in degrading adenosine and guanosine.The products of guanosine degraded by the Lactobacillus were guanine and hypoxanthine.(3)Analysis of the way to relieve hyperuricemia by Lactobacillus from the perspective of gut microbiota and SCFAs.The changes in gut microbiota and SCFAs levels of mice were analysed.The results showed that Lactobacillus rhamnosus CCFM1130,Lactobacillus rhamnosus CCFM1131 and Lactobacillus reuteri CCFM1132 increased the relative abundance of the genus such as Lactobacillus and SCFAs-producing bacteria(Ruminiclostridium 5,Ruminiclostridium 9 and Ruminococcaceae UCG 004),and increased the SCFAs concentrations in the caecal content of hyperuricaemia mice.The correlation analysis showed that the level of uric acid in serum and XOD activity were strongly correlated with the abundance of SCFAs-producing bacteria and SCFAs concentrations.It is speculated that Lactobacillus can relieve hyperuricaemia through increasing the level of SCFAs in the intestine by affecting the abundance level of SCFAs-related taxa.(6)Verifing whether SCFAs are the key effector molecules for Lactobacillus to relieve hyperuricemia.The inhibition effects of SCFAs on XOD activity was analyzed in vitro.The results showed that the ranking of activity inhibition effects of XOD were as follows: acetic acid < propionic acid < butyric acid < valeric acid.At the same time,the effects of different SCFAs on the hyperuricaemia of mice were analyzed through a technique that makes SCFAs released fixed-points in vivo.The results showed that acetic acid and valeric acid significantly relieved hyperuricaemia of mice,as reflected by reduced uric acid concentrations in serum and unine,suppressed serum and hepatic XOD activity,improved the elevated hepatic inflammation and renal injury,and changed gut microbiota in hyperuricaemia mice.Finally,it was speculated that Lactobacillus,especially Lactobacillus rhamnosus CCFM1130,Lactobacillus rhamnosus CCFM1131 and Lactobacillus reuteri CCFM1132,could alleviate hyperuricaemia by regulating the composition of gut microbiota and elevating the levels of SCFAs,especially acetic acid and valeric acid,in the large intestine,which coud suppress XOD activity and lead to the alleviation of hyperuricaemia.