Microbiota-Sourced Purines Support Wound Healing and Mucous Barrier Function

The intestinal mucosa requires high levels of nucleotides for energy procurement, proliferation, and innate immunity. This need for nucleotide substrates substantially increases during injury, infection, and wound healing. In the present studies, we profile potential sources of purine nucleotides in murine mucosal tissue. This work reveals the gut microbiota as a prominent source of exogenous purines and that such microbiota-sourced purines (MSPs) are available to the intestinal mucosa. The MSPs are utilized for nucleotide genesis and promote energy balance. Further analyses reveal that colitic tissues lacking MSPs are proliferatively stunted, with notable energetic and endoplasmic reticulum stress to the detriment of mucous barrier integrity. Purine reconstitution either directly or through colonization of germ-free/antibiotic-treated mice with MSP-sufficient E. coli alleviates such deficits, establishing MSP as a critical source of substrate for tissue metabolism, wound healing, and mucous barrier sterile integrity. [Display omitted] •The gut microbiota releases purine compounds available to the host mucosal tissue•Microbiota-sourced purines (MSPs) are salvaged by the gut mucosa for nucleotide genesis•MSPs support energy balance, proliferation, and mucous barrier function•Supplementation with hypoxanthine recapitulates the benefits afforded by MSPs Biochemistry; Immunology; Microbiology