Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model

Background: Intestinal microbiota is the primary target for the multifunctional nature of berberine. Berberine can reverse the structure and composition of gut microbiota under pathological conditions. This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate. Methods: Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. The alterations in gut microbiota were investigated using 16S rRNA sequencing. Results: The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans. Conclusion: Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota.