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Uric acid-inducible genes in bacteria from the human gut microbiome

ABSTRACT: Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the inflammatory 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 a substantial amount of uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here we identify a gene cluster, widely distributed in the gut microbiome, 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 such as acetate, lactate and butyrate. Ablation of the microbiota in uricase-deficient mice causes profound 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.

ORGANISM(S): Clostridium sporogenes ATCC 15579 Collinsella aerofaciens ATCC 25986 [Clostridium] saccharolyticum WM1

PROVIDER: GSE206419 | GEO | 2023/06/16

REPOSITORIES: GEO

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