Bacterial stimulation of endogenous hydrogen sulfide synthesis: a novel mechanism for resolution and repair in the colon

Hydrogen sulfide (H 2 S) is an important signaling molecule throughout the gastrointestinal (GI) tract. Colonic H 2 S synthesis is markedly increased during experimental colitis in rats, and contributes to the resolution of inflammation and healing of ulcers. The triggers responsible for this up‐regulation of colonic H 2 S synthesis are unclear. Therefore, we tested whether bacterial signals at the epithelial surface may be important stimuli for upregulation of endogenous H 2 S synthesis, helping drive resolution and mucosal repair. Germ‐free NIH Swiss mice (6 weeks of age; n≥4) were orally gavaged with feces (200 μL; 5% wt/ vol) from mice raised in specific pathogen free (SPF) conditions. Inoculated mice were housed in SPF conditions and euthanized at day 2 or 7 post‐inoculation. Colonic tissue from germ‐free control mice produced very low amounts of H 2 S. Within 2 days of inoculation with SPF flora, a significant increase in colonic H 2 S synthesis was observed (>;2‐fold; p<0.05), which further increased to 5‐fold (p<0.01) by 7 days post‐inoculation. We previously found that bacterial‐derived H 2 S does not contribute to what is measured as colonic H 2 S synthesis. These results support the hypothesis that bacterial factors can up‐regulate colonic H 2 S, which could be an important signaling mechanism for driving the repair of mucosal injury. Supported by the Crohn's and Colitis Foundation of Canada (CCFC).