Cell · 2023
A widely distributed gene cluster compensates for uricase loss in hominids.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Liu Yuanyuan, Jarman J Bryce, Low Yen S, Augustijn Hannah E, Huang Steven, Chen Haoqing, DeFeo Mary E, Sekiba Kazuma, Hou Bi-Huei, Meng Xiandong, Weakley Allison M, Cabrera Ashley V, Zhou Zhiwei, van Wezel Gilles, Medema Marnix H, Ganesan Calyani, Pao Alan C, Gombar Saurabh, Dodd Dylan
Аннотация
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.