The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia

Abstract

Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.

Keywords: Change; Correlation; Fecal microbiota transplantation; Gut microbiota; Gut microbiota disorder; Hyperuricemia.

Figure 1. Validating the HUA model and grouping of experimental animals.

(A) A boxplot showing uric acid content (n = 19 − 29); (B) Anosim analysis based on gut microbiota (n = 19 − 29), the R value correlation showing intra-group and inter-group differences. HUA, hyperuricemia group; N, normal group; Asterisks show any significant discrepancy by Student’s unpaired t-test; ***, P < 0.001.

Figure 2. Characteristic comparisons of the gut microbiota between the HUA and the N groups.

(A) the Shannon index (n = 19 − 29); (B) PCoA analyzing results (n = 19 − 29); (C) the microbial composition at phylum level (n = 19 − 29); (D) the relative abundance of three dominant phyla between the two groups (n = 19 − 29). HUA, hyperuricemia group; N, normal group. Data are represented as mean ± SD. Asterisks indicate the significance of discrepancy by Wilcoxon rank-sum test; ***, P < 0.001; **, P < 0.01 and *, P < 0.05.

Figure 3. Microbial taxa discrepancies between the HUA and the N rats.

(A) Histograms (n = 19 − 29); (B) Cladogram (n = 19 − 29); HUA, hyperuricemia group; N, normal group.

Figure 4. Analysis of biochemical indicators and gut microbiota in Ab-fed HUA rats (n = 3 − 8).

(A) UA, Uric acid; (B) Cr, Creatinine ; (C) BUN, Blood urea nitrogen; (D) HDL, high density lipoprotein; (E) LDL, low density lipoprotein; (F) Chao1; (G) PCoA analysis; N, normal group; HUA, hyperuricemia group; Ab+HUA, antibiotic-fed hyperuricemia group; Ab+N, antibiotic-fed normal group; dusty blue, pink, green and black asterisks indicate the significance of discrepancy between HUA and N, Ab+HUA and N, Ab+N and N, HUA and Ab+HUA, respectively; Data are represented as mean ± SD. Biochemical data and microbial data were compared using one-way ANOVA and Kruskal-Wallis test, respectively. Statistical significance is defined as *** P < 0.001, ** P < 0.01, * P < 0.05 and ns, no significant difference.

Figure 5. Establishing recipient rat model and similar microbiota between donors and recipient rats.

(A) and (B), the richness (Chao1) and diversity (Shannon) of gut microbiota in normal rats (week 0), pre- (week 1) and post-transplant recipient rats (week 5), respectively; (C) (D), the similar dominant phylum between donors and recipient rats; (E) and (F), the similar microbial abundance between donors and recipient rats; HUA and N donors, the fecal microbiota of HUA and N rats, respectively; HMT and NMT, hyperuricemia and normal microbiota transplantation group, respectively.

Figure 6. Biochemical analyses of fecal transplant recipient rats (n = 3 − 10).

Week 1, pre-transplant recipient rats; Week 3, 5 and 7, post-transplant recipient rats; (A), UA, uric acid; (B) Cr, Creatinine; (C) BUN, Blood urea nitrogen; (D) HDL, High density lipoprotein ; (E), LDL, Low density lipoprotein; NMT, normal microbiota transplantation group; HMT, hyperuricemia microbiota transplantation group; data are represented as mean ± SD. Asterisks, the significance of discrepancy between the HMT and the NMT groups by Student’s unpaired t-test, *, P < 0.05.