Hydrogen Sulfide Protects from Colitis and Restores Intestinal Microbiota Biofilm and Mucus Production. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Motta, Jean-Paul; Flannigan, Kyle L.; Agbor, Terence A.; Beatty, Jennifer K.; Blackler, Rory W.; Workentine, Matthew L.; Da Silva, Gabriela J.; Wang, Rui; Buret, Andre G.; Wallace, John L.
• Is Part Of: Inflammatory bowel diseases. Volume 21:Issue 5(2015:May)
• Publication Date: 2015-05
• Subjects: colitis -- hydrogen sulfide -- microbiota -- biofilm -- mucus -- IBD; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000345
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: Microbiota dysbiosis and impaired barrier function are among the most prominent features of inflammatory bowel disease. In the gastrointestinal tract, hydrogen sulfide (H2 S) is an important regulator of mucosal homeostasis. We hypothesized that H2 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 H2 S production (cystathionine γ-lyase) and pharmacologically inhibited that enzyme during colitis in wild-type mice. We tested the effects of administering an H2 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 H2 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 H2 S had beneficial effects on establishment of microbiota biofilms and colonic mucus production. Therapeutic delivery of H2 S into the colon reduced inflammation, restored the microbiota biofilm, and increased the production of mucus granules. In ex vivo human microbiota, H2 S not only promoted biofilm formation but also reduced growth of planktonic bacteria. Conclusions: Our results suggest that H2 S donors could be used therapeutically during colitis, facilitating correction of microbiota biofilm dysbiosis and mucus layer reconstitution. Abstract : Article first published online 3 March 2015.Supplemental Digital Content is Available in the Text.