广泛分布的基因簇补偿了灵长类动物尿酸酶的缺失。
A widely distributed gene cluster compensates for uricase loss in hominids.
机构信息
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Atropos Health, Palo Alto, CA, USA.
出版信息
Cell. 2023 Aug 3;186(16):3400-3413.e20. doi: 10.1016/j.cell.2023.06.010.
Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.
约 15%的美国成年人血液中的尿酸水平超过其溶解度极限，这与痛风病有因果关系。在大多数哺乳动物中，尿酸的排泄是由尿酸酶这种酶来促进的。然而，人类的尿酸酶是一个假基因，在人类进化的早期就已经失活了。尽管人们早就知道尿酸是在肠道中排出的，但肠道微生物群在高尿酸血症中的作用尚未得到研究。在这里，我们鉴定出一个广泛分布的细菌基因簇，它编码尿酸降解途径。稳定同位素示踪表明，肠道细菌将尿酸代谢为黄嘌呤或短链脂肪酸。在尿酸酶缺乏的小鼠中清除微生物群会导致严重的高尿酸血症，而针对厌氧菌的抗生素会增加人类患痛风的风险。这些数据揭示了肠道微生物群在尿酸排泄中的作用，并强调了针对微生物组的治疗方法在高尿酸血症中的潜力。
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