The Central Role of Gut Microbes in Host Purine Homeostasis

Purines are ubiquitous metabolites that play evolutionarily conserved roles, including as precursors to molecules central to life. Purine synthesis is metabolically and energetically expensive; thus, under physiological conditions, intermediates of purine degradation are efficiently reused through salvage pathways. Excess purines are oxidized and eliminated via the kidneys and intestine. The efficient elimination of excess purines in humans is critical because the primary waste product of purine metabolism, uric acid, is proinflammatory and has been linked to multiple health conditions. Recent studies suggest that gut bacteria influence the purine pool locally and systemically. Bacteria can break down uric acid and other purines aerobically and anaerobically and may regulate their homeostasis. In this article, we provide an overview of purines and their metabolism, and we discuss our current understanding of the complex purine-dependent cross talk and cross-feeding between the host and the gut microbiome.