1. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism.
- Author
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Fachi JL, Felipe JS, Pral LP, da Silva BK, Corrêa RO, de Andrade MCP, da Fonseca DM, Basso PJ, Câmara NOS, de Sales E Souza ÉL, Dos Santos Martins F, Guima SES, Thomas AM, Setubal JC, Magalhães YT, Forti FL, Candreva T, Rodrigues HG, de Jesus MB, Consonni SR, Farias ADS, Varga-Weisz P, and Vinolo MAR
- Subjects
- Administration, Oral, Animals, Anti-Bacterial Agents pharmacology, Butyrates pharmacology, Clostridioides difficile metabolism, Colitis etiology, Colitis microbiology, Epithelial Cells cytology, Epithelial Cells drug effects, Epithelial Cells metabolism, Fatty Acids, Volatile metabolism, Humans, Insulin administration & dosage, Intestinal Mucosa cytology, Intestinal Mucosa pathology, Male, Mice, Mice, Inbred C57BL, Microbiota drug effects, Permeability drug effects, Tight Junctions metabolism, Toxins, Biological toxicity, Triglycerides administration & dosage, Butyrates administration & dosage, Clostridioides difficile pathogenicity, Colitis prevention & control, Hypoxia-Inducible Factor 1 metabolism
- Abstract
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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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