Microbiota-Sourced Purines Support Wound Healing and Mucous Barrier Function

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• Intestinal mucosa relies on nucleotides for energy, proliferation, and immunity.
• These needs increase significantly during injury, infection, and wound healing.

Purpose of the Study:

• To identify sources of purine nucleotides in murine intestinal tissue.
• To investigate the role of microbiota-sourced purines (MSPs) in intestinal health and repair.

Main Methods:

• Profiling purine nucleotide sources in murine mucosal tissue.
• Assessing the impact of MSP deficiency and repletion on colitic tissues.
• Utilizing germ-free and antibiotic-treated mice colonized with specific E. coli strains.

Main Results:

• The gut microbiota is a significant source of exogenous purines (MSPs) available to the intestinal mucosa.
• MSPs are utilized for nucleotide synthesis, promoting energy balance and tissue proliferation.
• Colitic tissues lacking MSPs exhibit impaired proliferation, energetic deficits, and endoplasmic reticulum stress, compromising barrier integrity.

Conclusions:

• Microbiota-sourced purines (MSPs) are critical substrates for intestinal metabolism, wound healing, and maintaining mucous barrier integrity.
• Restoring MSPs, directly or via microbial colonization, alleviates deficits in colitic tissues.