Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout patients and 86 healthy controls. Gout metagenomes significantly differed from those of healthy controls. The relative abundances of Prevotella, Fusobacterium, and Bacteroides were increased in gout, whereas those of Enterobacteriaceae and butyrate-producing species were decreased. Functionally, gout patients had greater abundances for genes in fructose, mannose metabolism and lipid A biosynthesis, and lower for genes in urate degradation and short chain fatty acid production. A three-pronged association between metagenomic species, functions and clinical parameters revealed that decreased abundances of species in Enterobacteriaceae were associated with reduced amino acid metabolism and environmental sensing, which together contribute to increased serum uric acid and C-reactive protein levels in gout. A random forest classifier based on three gut microbial genes showed high predictivity for gout in both discovery and validation cohorts (0.91 and 0.80 accuracy), with high specificity in the context of other chronic disorders. Longitudinal analysis showed that uric-acid-lowering and anti-inflammatory drugs partially restored gut microbiota after 24-week treatment. Comparative analysis with obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis indicated that gout metagenomes were more similar to those of autoimmune than metabolic diseases. Our results suggest that gut dysbiosis was associated with dysregulated host urate degradation and systemic inflammation and may be used as non-invasive diagnostic markers for gout.

新出现的证据表明肠道微生物群与包括痛风在内的关节炎疾病之间存在关联。然而，肠道细菌如何以及哪些肠道细菌影响痛风中的宿主尿酸盐降解和炎症仍不清楚。在这里，我们对来自 102 名痛风患者和 86 名健康对照者的 307 份粪便样本进行了宏基因组分析。痛风宏基因组与健康对照组显着不同。痛风中普氏菌属、梭杆菌属和拟杆菌属的相对丰度增加，而肠杆菌科的相对丰度增加。和产生丁酸盐的物种减少。在功能上，痛风患者在果糖、甘露糖代谢和脂质 A 生物合成中的基因丰度更高，而在尿酸盐降解和短链脂肪酸产生中的基因丰度较低。宏基因组物种、功能和临床参数之间的三管齐下的关联表明，肠杆菌科细菌的物种丰度降低与减少氨基酸代谢和环境感知有关，这共同有助于增加痛风中的血清尿酸和 C 反应蛋白水平。基于三个肠道微生物基因的随机森林分类器在发现和验证队列中显示出对痛风的高度预测（0.91 和 0.80 准确度），在其他慢性疾病的背景下具有高度特异性。纵向分析显示，降尿酸和抗炎药物在治疗 24 周后部分恢复了肠道菌群。与肥胖、2型糖尿病、强直性脊柱炎和类风湿性关节炎的比较分析表明，痛风的宏基因组更类似于自身免疫性疾病而不是代谢性疾病。