The relationship between intestinal bacteria and hyperuricemia is a hot research topic. To better understand this relationship, uricase-deficient Sprague–Dawley rats (Kunming-DY rats) were used. The wild-type rats and Kunming-DY rats were used as controls. Kunming-DY rats were treated with ampicillin (90 mg/kg) and ciprofloxacin (150 mg/kg) for 5 days. Bacterial 16S rDNA in the fresh stool was sequenced, and the abundance was calculated. The rats’ serum uric acid (SUA) level was assayed, and the rats’ intake and output in 24 h were recorded. The bacterial diversity in three groups’ fresh stool was analyzed. The gut bacterial diversity and abundance changed in the Kunming-DY rats. More than 99% of bacteria were inhibited or killed by the combination of antibiotics. In contrast to each of the antibiotics alone, the combination of antibiotics lowered the Kunming-DY rats’ SUA level; it also caused mild diarrhea, which increased uric acid excretion through stool. These results suggested that the aboriginal gut bacteria in uricase-deficient rats play a minor role in determining the SUA levels. It is too early to conclude that aboriginal gut bacteria are a tempting target for lowering SUA levels.

The aim of this study was to provide a sensitive model animal for studying hyperuricemia. Male uricase-deficient rats, named Kunming-DY rats, were raised for 130 days, or orally administered with purines and other chemicals. Serum uric acid (SUA) in the animals was assayed, and the UA level in their organs and their 24-h excretion was determined. Genes in the jejunum, ileum, kidney and liver related to UA synthesis and transportation were detected by quantitative RNA sequencing. Uricase-deficient rats have a high level of SUA and are sensitive to xanthine, adenosine, inosine, allopurinol, and alcohol. Besides, the high level of SUA in male uricase-deficient rats was stable, much higher than that in wild-type rats but similar to that in men. The distribution pattern of UA in uricase-deficient rats’ organs was different from that in wild-type rats. The kidney, liver, and small intestine were the top three organs where UA distributed, but the UA in the small intestine, colon, lung, thymus, and brain was less affected by uricase deficiency, indicating that these organs are constitutive distribution organs in UA. The 24-h UA excreted by a uricase-deficient rat was about five times higher than that excreted by a wild-type rat. However, the 24-h UA excreted through feces was not significantly changed. Both the urine volume and UA in uricase-deficient rats significantly increased, and more than 90% of UA was excreted via urine. The expression of xanthine dehydrogenase was not upregulated. Some genes of transporter associated with uric acid excretion in the kidney were significantly regulated, though not sufficient to explain the increase in SUA. In conclusion, male uricase-deficient rats’ UA metabolism is similar to that of men. The elevation of SUA in uricase-deficient rats is caused by uricase deficiency, and uricase-deficient rats are a sensitive model for studying hyperuricemia.