Gut bacterial metabolism contributes to host global purine homeostasis

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.

Automated summary

The study suggests that gut microbiota plays a role in the progression of inflammatory diseases such as atherosclerosis. It shows that certain gut bacteria can use uric acid as a carbon and energy source, and their catabolism of purines influences the levels of uric acid in the body. This highlights the importance of gut microbes in maintaining purine homeostasis and overall health.