Alterations of the Gut Microbiome Associated With the Treatment of Hyperuricaemia in Male Rats

Abstract

Hyperuricaemia is an important risk factor for many diseases including gout, hypertension, and type II diabetes. The gut microbiota is associated with hyperuricaemia and has also been demonstrated to play significant roles in the effects of drug therapy. This study used Illumina MiSeq sequencing to explore alterations of the gut microbiome associated with allopurinol and benzbromarone treatment in the male rat with hyperuricaemia. After drug treatment, both allopurinol and benzbromarone caused an increase of the genera Bifidobacterium and Collinsella and a decrease of the genera Adlercreutzia and Anaerostipes. In addition, allopurinol and benzbromarone caused respective unique changes in genera. The genera Bilophila, Morganella, and Desulfovibrio specifically decreased due to allopurinol treatment. Decreased Butyricimonas and Ruminococcus and increased Proteus were caused by benzbromarone treatment. The PICRUST analysis indicated that allopurinol renovated the disorder of nucleotide metabolism and benzbromarone renovated the disorder of lipid metabolism in the gut microbiota of male rats with hyperuricaemia. These findings demonstrated that the gut microbiota may be altered by the treatment of hyperuricaemia with allopurinol and benzbromarone in male rats. Such alterations of the gut microbiota could be considered as indicators of the effectiveness of drug therapy.

Keywords: Illumina MiSeq; allopurinol; benzbromarone; gut microbiome; hyperuricaemia.

FIGURE 1

Serum uric acid (A), creatinine (B), glutamic oxaloacetic transaminase (C) and cholesterol (D) levels of male rats in four treatment groups. “^∗” represents the adjusted p value <0.05 between two groups; “^∗∗” represents the adjusted p value <0.01 between two groups; “ND” represents the adjusted p value >0.05 between groups.

FIGURE 2

Alpha diversity indices [Shannon (A); PD Whole Tree (B)] and Beta diversity [PCoA score plots (C); unweighted UniFrac distance (D)] of male rats in the four groups. “^∗” represents the adjusted p value <0.05 between two groups; “^∗∗” represents the adjusted p value <0.01 between two groups; “ND” represents the adjusted p value >0.05 between groups.

FIGURE 3

Differentially expressed taxa with the LDA scores >2.0 and adjusted p values <0.05 between the control rats and model rats. Differences are represented by the color of over-represented taxa: red indicating the control rats, green indicating the model rats. Circles represent phylogenetic levels from phylum (innermost circle) to genera (outermost circle).

FIGURE 4

Differentially expressed taxa with the LDA scores >2.0 and adjusted p values <0.05 between the model rats and allopurinol-treated rats (A), and between the model rats and benzbromarone-treated rats (B). Differences are represented by the color of over-represented taxa: red indicating the allopurinol-treated rats or the benzbromarone-treated rats, green indicating the model rats. Circles represent phylogenetic levels from phylum (innermost circle) to genera (outermost circle).

FIGURE 5

Venn diagram showing the distribution of shared and unique microbial genera in the control vs model, allopurinol vs model, and benzbromarone vs model comparisons.

FIGURE 6

Predicted microbial functions comparisons. Gene functional categories were from level 2 of KEGG pathways. Gene functions with a significant difference are shown (adjusted p value <0.05). (A) Comparing microbial function between the control rats and model rats, the enriched functions in the control rats are shown with red color and the enriched functions in the model rats are shown with green color. (B) Comparing microbial function the model rats and allopurinol-treated rats, the enriched functions in the allopurinol-treated rats are shown with red color and the enriched functions in the model rats are shown with green color. (C) Comparing microbial function between the model rats and benzbromarone-treated rats, the enriched functions in the benzbromarone-treated rats are shown with red color and the enriched functions in the model rats are shown with green color.