Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production

Abstract

Background: Microbiota dysbiosis and impaired barrier function are among the most prominent features of inflammatory bowel disease. In the gastrointestinal tract, hydrogen sulfide (H 2 S) is an important regulator of mucosal homeostasis. We hypothesized that H 2 S promotes resolution of colonic inflammation through actions on microbiota biofilm and the mucus barrier. Methods: We used mice genetically deficient for a key enzyme for H 2 S production (cystathionine γ-lyase) and pharmacologically inhibited that enzyme during colitis in wild-type mice. We tested the effects of administering an H 2 S donor (diallyl disulfide) to rodents during hapten-induced colitis. Colonic microbiota biofilm was visualized by fluorescent in situ hybridization, and mucus granules were quantified with periodic acid-alcian blue staining. We exposed human microbiota biofilms and planktonic bacteria to H 2 S donors ex vivo to determine changes in their growth, viability, and biomass. Results: Intestinal microbiota formed linear biofilms in the colon of healthy rodents. During colitis, microbiota biofilms were fragmented and mucus granule production decreased. Endogenous production of H 2 S had beneficial effects on establishment of microbiota biofilms and colonic mucus production. Therapeutic delivery of H 2 S into the colon reduced inflammation, restored the microbiota biofilm, and increased the production of mucus granules. In ex vivo human microbiota, H 2 S not only promoted biofilm formation but also reduced growth of planktonic bacteria. Conclusions: Our results suggest that H 2 S donors could be used therapeutically during colitis, facilitating correction of microbiota biofilm dysbiosis and mucus layer reconstitution.