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.
Highlights
Hyperuricaemia is characterized by the elevation of blood uric acid (UA) caused by disordered purine metabolism
Value
The gut microbiota has emerged as an important contributor to hyperuricaemia, and it has been shown to impact the response to disease treatment
Summary
Hyperuricaemia is characterized by the elevation of blood uric acid (UA) caused by disordered purine metabolism. Hyperuricaemia is considered to be a metabolic problem, and its associations with many diseases have been observed for decades. These diseases include gout (Bardin and Richette, 2014), cardiovascular disease (Yang et al, 2012; Li et al, 2014), chronic renal disease (Talaat and el-Sheikh, 2007), and type 2 diabetes (Mantovani et al, 2016). Allopurinol and benzbromarone are two common urate-reducing drugs with different mechanisms of action. Allopurinol is an effective xanthine oxidase inhibitor that blocks UA production (Kim et al, 2015), while benzbromarone is a uricosuric agent that promotes UA excretion (Kunishima et al, 2007). It is well known that the gut microbiome could be partially responsible for converting xanthine into UA (Barsoum and El-Khatib, 2017) and excreting 1/3 of
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