美国斯坦福大学医学院Dylan Dodd研究组发现，分布广泛的基因簇弥补人类尿酸酶的缺失。该研究于2023年8月3日发表于国际一流学术期刊《细胞》。

研究人员发现了一个广泛分布的细菌基因簇，它编码了尿酸降解的途径。稳定同位素追踪表明，肠道细菌可将尿酸代谢为黄嘌呤或短链脂肪酸。尿酸酶缺陷小鼠的微生物群去除会导致严重的高尿酸血症，而厌氧菌靶向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，并强调了微生物群靶向治疗高尿酸血症的潜力。

据介绍，大约15%的美国成年人血液循环中的尿酸水平超过了其溶解极限，这与痛风病有因果关系。在大多数哺乳动物体内，尿酸是通过尿酸酶排出体外的。然而，人类的尿酸酶是一种假基因，在人类演化的早期就已经失活。虽然人们早就知道尿酸是通过肠道排出的，但对肠道微生物群在高尿酸血症中的作用还没有进行过研究。

附：英文原文

Title: A widely distributed gene cluster compensates for uricase loss in hominids

Author: Yuanyuan Liu, J. Bryce Jarman, Yen S. Low, Hannah E. Augustijn, Steven Huang, Haoqing Chen, Mary E. DeFeo, Kazuma Sekiba, Bi-Huei Hou, Xiandong Meng, Allison M. Weakley, Ashley V. Cabrera, Zhiwei Zhou, Gilles van Wezel, Marnix H. Medema, Calyani Ganesan, Alan C. Pao, Saurabh Gombar, Dylan Dodd

Issue&Volume: 2023/08/03

Abstract: Approximately 15% of US adults have circulating levels of uric acid above its solubilitylimit, which is causally linked to the disease gout. In most mammals, uric acid eliminationis facilitated by the enzyme uricase. However, human uricase is a pseudogene, havingbeen inactivated early in hominid evolution. Though it has long been known that uricacid is eliminated in the gut, the role of the gut microbiota in hyperuricemia hasnot been studied. Here, we identify a widely distributed bacterial gene cluster thatencodes a pathway for uric acid degradation. Stable isotope tracing demonstrates thatgut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablationof the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targetedantibiotics increase the risk of gout in humans. These data reveal a role for thegut microbiota in uric acid excretion and highlight the potential for microbiome-targetedtherapeutics in hyperuricemia.

DOI: 10.1016/j.cell.2023.06.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00687-6