Gut bacterial metabolism contributes to host global purine homeostasis

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  • Kazuyuki Kasahara
  • Robert L. Kerby
  • Qijun Zhang
  • Meenakshi Pradhan
  • Margarete Mehrabian
  • Aldons J. Lusis
  • Göran Bergström
  • Fredrik Bäckhed
  • Federico E. Rey

The microbes and microbial pathways that influence host inflammatory disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden is partially driven by gut microbiota and is associated with circulating levels of uric acid (UA) in mice and humans. We identify gut bacterial taxa spanning multiple phyla, including Bacillota, Fusobacteriota, and Pseudomonadota, that use multiple purines, including UA as carbon and energy sources anaerobically. We identify a gene cluster that encodes key steps of anaerobic purine degradation and that is widely distributed among gut-dwelling bacteria. Furthermore, we show that colonization of gnotobiotic mice with purine-degrading bacteria modulates levels of UA and other purines in the gut and systemically. Thus, gut microbes are important drivers of host global purine homeostasis and serum UA levels, and gut bacterial catabolism of purines may represent a mechanism by which gut bacteria influence health.

Original languageEnglish
JournalCell Host and Microbe
Volume31
Issue number6
Pages (from-to)1038-1053.e10
ISSN1931-3128
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

    Research areas

  • atherosclerosis, gut microbiome, purines, uric acid

ID: 360980070