Fachi, Jose LuisFelipe, Jaqueline de SouzaPral, Lais Passarielloda Silva, Bruna KaradiCorrea, Renan OliveiraPereira de Andrade, Mirella Cristinyda Fonseca, Denise MoraisBasso, Paulo JoseSaraiva Camara, Niels Olsende Sales e Souza, Ericka LorennaMartins, Flaviano dos SantosSato Guima, Suzana EikoThomas, Andrew M.Setubal, Joao CarlosMagalhaes, Yuli ThamiresForti, Fabio LuisCandreva, ThamirisRodrigues, Hosana Gomesde Jesus, Marcelo BispoConsonni, Silvio RobertoFarias, Alessandro dos SantosVarga-Weisz, PatrickRamirez Vinolo, Marco Aurelio2019-08-212019-08-212019-04-162211-1247http://hdl.handle.net/10919/93202Antibiotic-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.application/pdfenCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalArticle - Refereedhttps://doi.org/10.1016/j.celrep.2019.03.05430995474