Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism
Open accessAbstract
Antibiotic-induced dysbiosis is a key factor predisposing intestinal infection by Clostridium difficile. Here, we show that interventions that restore butyrate intestinal levels mitigate clinical and pathological features of C. difficile-induced colitis. Butyrate has no effect on C. difficile colonization or toxin production. However, it attenuates intestinal inflammation and improves intestinal barrier function in infected mice, as shown by reduced intestinal epithelial permeability and bacterial translocation, effects associated with the increased expression of components of intestinal epithelial cell tight junctions. Activation of the transcription factor HIF-1 in intestinal epithelial cells exerts a protective effect in C. difficile-induced colitis, and it is required for butyrate effects. We conclude that butyrate protects intestinal epithelial cells from damage caused by C. difficile toxins via the stabilization of HIF-1, mitigating local inflammatory response and systemic consequences of the infection.
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Butyrate and valerate promote intestinal barrier function, which prevents the translocation of pathogens from the intestine into the bloodstream.
“Butyrate and valerate promote intestinal barrier function, which prevents the translocation of pathogens from the intestine into the bloodstream [45–48].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [48]
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- Authors
- Fachi, J. L., Felipe, J. D. S., Pral, L. P., da Silva, B. K., Corrêa, R. O., de Andrade, M. C. P., da Fonseca, D. M., Basso, P. J., Câmara, N. O. S., de Sales e Souza, É. L., dos Santos Martins, F., Guima, S. E. S., Thomas, A. M., Setubal, J. C., Magalhães, Y. T., Forti, F. L., Candreva, T., Rodrigues, H. G., de Jesus, M. B., Consonni, S. R., Farias, A. D. S., Varga-Weisz, P., & Vinolo, M. A. R.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Universidade de São Paulo (BR)
- Corresponding author
- Vinolo, Marco Aurélio Ramirez
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 27
- Issue
- 3
- Pages
- 750-761.e7
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2940220885
- Cited by
- 364
- References
- 53
- Citations by year
- 2026: 42 · 2025: 53 · 2024: 54 · 2023: 59 · 2022: 53 · 2021: 57 · 2020: 36 · 2019: 10
- FWCI
- 29.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Open Access at Essex (University of Essex) (acceptedVersion)
- VTechWorks (Virginia Tech) (submittedVersion, cc-by-nc-nd)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Royal Society
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/10653-9, 2013/06810-4, 2014/03002-7, 2015/06134-4, 2017/16280-3, 2018/01753-6)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- butyrate, Clostridium difficile, colitis, HIF-1, intestinal epithelial cells, tight junctions, intestinal barrier function, intestinal permeability, bacterial translocation, intestinal inflammation, antibiotic-induced dysbiosis, C. difficile toxin, gut microbiota
- MeSH terms
- Administration, Oral, Animals, Anti-Bacterial Agents, Butyrates, Colitis, Epithelial Cells, Fatty Acids, Volatile, Humans, Insulin, Intestinal Mucosa, Male, Mice, Inbred C57BL, Permeability, Toxins, Biological, Triglycerides, Clostridioides difficile, Tight Junctions, Mice, Hypoxia-Inducible Factor 1, Microbiota
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