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.
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Lower concentrations of endogenously derived H2S exert beneficial cytoprotective, antioxidant and anti-inflammatory actions.
“On one hand, it appears that lower concentrations of endogenously derived H2S exert beneficial cytoprotective, antioxidant and anti-inflammatory actions[344,348–351]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [350]
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- Authors
- Motta, J.-P., Flannigan, K. L., Agbor, T. A., Beatty, J. K., Blackler, R. W., Workentine, M. L., Da Silva, G. J., Wang, R., Buret, A. G., & Wallace, J. L.
- Affiliations
- University of Calgary (CA)
- McMaster University (CA)
- Department of Biological Sciences (RU)
- Lakehead University (CA)
- Venue
- Inflammatory Bowel Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05
- Volume
- 21
- Issue
- 5
- Pages
- 1006-1017
- ISSN
- 1078-0998 (ISSN-L)
- OpenAlex
- W2000311257
- Semantic Scholar
- bb2c3441ef0a8ec830e08d39ef35f3594ac2ef26
- Cited by
- 200
- References
- 52
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 24 · 2023: 24 · 2022: 18 · 2021: 18 · 2020: 15 · 2019: 15 · 2018: 11 · 2017: 16 · 2016: 16 · 2015: 12 · 2014: 3
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Inflammatory Bowel Diseases (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- hydrogen sulfide, colitis
- MeSH terms
- Gastrointestinal Microbiome, Animals, Colitis, Humans, Hydrogen Sulfide, Intestinal Mucosa, Male, Mice, Inbred C57BL, Mucus, Dextran Sulfate, Rats, Wistar, In Situ Hybridization, Fluorescence, Biofilms, Mice, Rats, Gasotransmitters
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