1. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism
- Author
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Fachi, José Luís, Felipe, Jaqueline de Souza, Pral, Laís Passariello, da Silva, Bruna Karadi, Corrêa, Renan Oliveira, de Andrade, Mirella Cristiny Pereira, da Fonseca, Denise Morais, Basso, Paulo José, Câmara, Niels Olsen Saraiva, de Sales e Souza, Éricka Lorenna, dos Santos Martins, Flaviano, Guima, Suzana Eiko Sato, Thomas, Andrew Maltez, Setubal, João Carlos, Magalhães, Yuli Thamires, Forti, Fábio Luis, Candreva, Thamiris, Rodrigues, Hosana Gomes, de Jesus, Marcelo Bispo, Consonni, Sílvio Roberto, Farias, Alessandro dos Santos, Varga-Weisz, Patrick, and Vinolo, Marco Aurélio Ramirez
- 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. difficilecolonization 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. difficiletoxins via the stabilization of HIF-1, mitigating local inflammatory response and systemic consequences of the infection.
- Published
- 2019
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