Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism.
Cell Rep
; 27(3): 750-761.e7, 2019 04 16.
Article
in En
| MEDLINE
| ID: mdl-30995474
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Butyrates
/
Clostridioides difficile
/
Colitis
/
Hypoxia-Inducible Factor 1
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell Rep
Year:
2019
Document type:
Article
Affiliation country:
Brasil
Country of publication:
Estados Unidos