Ying Ying, Zhang Yi, Sun Jing, Chen Yong, Wu Huaxiang
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Rheumatology, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China.
Heliyon. 2024 Nov 29;10(23):e40597. doi: 10.1016/j.heliyon.2024.e40597. eCollection 2024 Dec 15.
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.
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.
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.
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.
探讨肥胖合并高尿酸血症（HUA-W）患者肠道菌群的结构特征及其促进高尿酸血症形成的机制。
收集120份人类粪便样本（健康对照（HC）60例、非肥胖高尿酸血症（HUA-N）30例、肥胖合并高尿酸血症（HUA-W）30例）以及40份结肠组织样本（HC 20例、HUA-N 10例、HUA-W 10例）。采用16s rRNA方法检测粪便中的肠道菌群；采用RT-qPCR法和免疫荧光法检测人结肠组织中SLC2A9的表达。建立40只肥胖高尿酸血症大鼠模型（模型组10只、HC-FT组10只、HUA-N-FT组10只、HUA-W-FT组10只），设正常对照组10只；检测大鼠血清尿酸水平、肠液中黄嘌呤氧化酶（XOD）活性及尿酸水平。构建SLC2A9 Caco-2细胞模拟Transwell尿酸转运模型，将Caco-2细胞和SLC2A9 Caco-2细胞在5种不同培养基（空白、无菌、HC-菌、HUA-N-菌、HUA-W-菌）中培养，检测小室上下层尿酸水平。
HUA-W肠道菌群具有显著特异性，拟杆菌门和拟杆菌纲减少，大肠杆菌和瘤胃球菌增加。HUA-N和HUA-W结肠组织中SLC2A9蛋白荧光强度及SLC2A9 mRNA水平差异无统计学意义（分别为=0.447，=0.152，=0.4799，=0.965）。在大鼠动物实验中，HUA-W-FT组肠液中尿酸水平显著升高（<0.05），XOD活性显著升高（<0.05）。在SLC2A9 Caco-2细胞的Transwell实验中，HUA-W-菌组上室尿酸水平升高，下室尿酸水平降低。
HUA-W肠道菌群可能增加肠道XOD活性，提高尿酸转运蛋白SLC2A9重吸收尿酸的能力，为高尿酸血症的发病机制提供了新的理论依据。
