Browsing by Author "da Fonseca, Denise Morais"

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    Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism
    Fachi, Jose Luis; Felipe, Jaqueline de Souza; Pral, Lais Passariello; da Silva, Bruna Karadi; Correa, Renan Oliveira; Pereira de Andrade, Mirella Cristiny; da Fonseca, Denise Morais; Basso, Paulo Jose; Saraiva Camara, Niels Olsen; de Sales e Souza, Ericka Lorenna; Martins, Flaviano dos Santos; Sato Guima, Suzana Eiko; Thomas, Andrew M.; Setubal, Joao Carlos; Magalhaes, Yuli Thamires; Forti, Fabio Luis; Candreva, Thamiris; Rodrigues, Hosana Gomes; de Jesus, Marcelo Bispo; Consonni, Silvio Roberto; Farias, Alessandro dos Santos; Varga-Weisz, Patrick; Ramirez Vinolo, Marco Aurelio (Cell Press, 2019-04-16)
    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.