E. coli genetically modified for purine nucleobase release promotes butyrate generation and colonic wound healing during DSS insult.

The gut microbiota transforms energy stored as undigestible carbohydrates into a remarkable number of metabolites that fuel intestinal bacterial communities and the host tissue. Colonic epithelial cells at the microbiota-host interface depend upon such microbiota-derived metabolites (MDMs) to satisfy their energy requisite. Microbial dysbiosis eliciting MDM loss contributes to barrier dysfunction and mucosal disease. Recent work has identified a role for microbiota-sourced purines (MSPs), notably hypoxanthine, as an MDM salvaged by the colonic epithelium for nucleotide biogenesis and energy balance. Here, we investigated the role of MSPs in mice during disease-modeled colonic energetic stress using a strain of E. coli genetically modified for enhanced purine nucleobase release (E. coli Mutant). E. coli Mutant colonization protected against DSS-induced tissue damage and permeability while promoting proliferation for wound healing. Metabolite and metagenomic analyses suggested a colonic butyrate-purine nucleobase metabolic axis, wherein the E. coli Mutant provided purine substrate for Clostridia butyrate production and host purine salvage, altogether supplying the host substrate for efficient nucleotide biogenesis and energy balance.