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A widely distributed gene cluster compensates for uricase loss in hominids.
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.
Afiliação
  • Liu Y; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Jarman JB; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Low YS; Atropos Health, Palo Alto, CA, USA.
  • Augustijn HE; Bioinformatics Group, Wageningen University, Wageningen, the Netherlands; Institute of Biology, Leiden University, Leiden, the Netherlands.
  • Huang S; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Chen H; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • DeFeo ME; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Sekiba K; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Hou BH; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Meng X; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.
  • Weakley AM; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.
  • Cabrera AV; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.
  • Zhou Z; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • van Wezel G; Institute of Biology, Leiden University, Leiden, the Netherlands; Netherlands Institute of Ecology, Wageningen, the Netherlands.
  • Medema MH; Bioinformatics Group, Wageningen University, Wageningen, the Netherlands; Institute of Biology, Leiden University, Leiden, the Netherlands.
  • Ganesan C; Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Pao AC; Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Gombar S; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Atropos Health, Palo Alto, CA, USA.
  • Dodd D; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: ddodd2@stanford.edu.
Cell ; 186(16): 3400-3413.e20, 2023 08 03.
Article em En | MEDLINE | ID: mdl-37541197
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hominidae / Hiperuricemia / Gota Limite: Adult / Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hominidae / Hiperuricemia / Gota Limite: Adult / Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos