Gut Miocrobiota Associated With Hyperuricemia

Hyperuricemia is a kind of metabolic disease, which due to purine metabolic disorder and the body produce too much uric acid or excretion decrease, resulting increase of serum uric acid level. Epidemiologic studies have suggested that the incidence of hyperuricemia have risen over the last few decades, which affects patients" quality of life and work. Gut microbiota play vital role in the occuress and progress of the metabolic disease-hyperuricemia.Firstly, hyperuricemia rat model and hyperuricemia mouse model were designed, gut microbiota were then seperated. Fecal microbiota transplantation mice model was made by gavaging fecal microbiota into germ-free mice. The study selected 40 male germ-free ICR mice as the research objects, which divided into three groups:the rat intestinal group (group R) containing 12 mice, the mouse intestinal group (group M) containing 12 mice, the control group (group C) containing16 mice. Biochemical indexes (UA, CRE, BUN, TG, TC, ALT, AST) and metabolic indexes (body weight,24 h food intake,24h urine volume and 24 h water intake) of each group were monitored and fecal genome DN A of microbiota colonized mice model were extracted, and then the V1-V3 region of 16s rRNA gene was sequenced by the barcode 454 sequencing technology. Optimized data were analyzed by OTU clustering and classification.During the five weeks of microbiota colonization, metabolic results indicated the difference among the 3 groups in the body weight,24 h food intake,24h urine volume and 24 h water intake were insignificant (p<0.05). The blood biochemical indexes and blood glucose values exhisted remarkable change after five weeks of microbiota colonization. According to blood biochemical examination results, TG of group R is significantly higher than that of group C, but the rest of biochemical indicators have no difference among three groups. Glucose tolerance results showed the blood glucose of group R is much higher than group C when glucose loaded 30 min (p<0.05). Besides, the blood glucose of group R and group M are significantly higher than group C when glucose loaded 60,90,120 min (p<0.05), which indicated the abnormal in glucose metabolism may attributed to fecal bacterial colonization.Microbiota 16S rRNA gene V1-V3 region sequencing results displayed a total of 205,338 optimal sequences have received, up to 91,817,752 bp. Coverage of constructed library is up to 99% and the sparse curve tended to flat with the increase of sequencing depth, which indicated the database is sufficient enough so that it can represent the vast majority of intestinal bacteria groups in our experimental animals. Furthermore, the sample size is sufficient to conduct data analysis. Community component analyse showed the difference of bacterial flora distribution in group M and group R is not significant in the genus level, and bacterial flora structure tends to be stable with colonization time increase. Principal component analysis showed that different microbiota colonization may be an important factor to lead group M separate from group R (35.68%), while different microbiota colonization may result in group M separating from group R (6.3%). According to the tree diagram, the similarity between group M and group R is lower than that of samples within the two groups, and the similarity between the two groups tends to be stable with colonization time increase.All experiment above indicated that the effect on fecal bacteria colonization in germ-free mice of blood glucose and blood lipid is matching the abnormal occurrence of blood glucose and blood lipid in patients with hyperuricemia clinically. Microbiota ecological analysis showed that microbiota structure reached a relatively stable state after 2 weeks of colonization. Gut microbiota colonization may lead to a significant difference in structure and diversity in model group, and colonization different gut microbiota may cause different influence to animal models.