Mechanism of intestinal flora affecting SLC2A9 transport function to promote the formation of hyperuricemia.

Objective: To investigate the structural characteristics of the intestinal flora in obese-hyperuricemic (HUA-W) patients and the mechanisms by which they promote the formation of hyperuricemia.

Methods: 120 human fecal samples (60 cases in HC, 30 cases in HUA-N, and 30 cases in HUA-W) and 40 cases in the colonic tissues (20 cases in HC, 10 cases in HUA-N, and 10 cases in HUA-W) were collected. The intestinal flora of faeces was detected by 16s rRNA method; and the expression of SLC2A9 on human colon tissues was detected by RT-qPCR method and immunofluorescence method. 40 obese-hyperuricemia rat models were established (10 rats in Model, 10 rats in HC-FT, 10 rats in HUA-N-FT, and 10 rats in HUA-W-FT), and 10 rats were set up in Control; and the level of uric acid in rat serum, the levels of xanthine oxidase (XOD) activity and uric acid in intestinal fluid were examined. SLC2A9 Caco-2 cells were produced to simulate the Transwell uric acid transport model, and the Caco-2 cells and SLC2A9 Caco-2 cells were grown in five different culture media (Blank, Germ-free, HC-germ, HUA-N-germ and HUA-W-germ), and the uric acid levels in the upper and lower layers of the chambers were detected.

Results: The HUA-W intestinal flora showed significant specificity, with a decrease in Bacteroidota and Bacteroidia and an increase in Escherichia and Ruminococcus. There were no significant differences in the fluorescence intensity of the SLC2A9 protein and the SLC2A9 mRNA levels in the colon tissues of the HUA-N and HUA-W ( = 0.447,  = 0.152,  = 0.4799 and  = 0.965, respectively). In rat animal experiments, uric acid levels were significantly higher ( < 0.05) and XOD activity was significantly higher ( < 0.05) in intestinal fluid of HUA-W-FT. In Transwell experiments with SLC2A9 Caco-2 cells, uric acid levels were increased in the upper compartment and decreased in the lower compartment of HUA-W-germ.

Conclusion: HUA-W intestinal flora may increase XOD activity in the intestinal tract and improve the ability of uric acid transporter protein SLC2A9 to reabsorb uric acid, providing a new theoretical basis for the pathogenesis of hyperuricemia.