Microbiota-Sourced Purines Support Wound Healing and Mucous Barrier Function

J. Scott Lee, Ruth X. Wang, Matthew S. Goldberg, Garrett P. Clifford, Daniel J. Kao, Sean P. Colgan

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish
Article number101226
JournaliScience
Volume23
Issue number6
DOIs
StatePublished - 26 Jun 2020
Externally publishedYes

Keywords

  • Biochemistry
  • Immunology
  • Microbiology

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