Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism

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dc.contributor.authorFachi, Jose Luisen
dc.contributor.authorFelipe, Jaqueline de Souzaen
dc.contributor.authorPral, Lais Passarielloen
dc.contributor.authorda Silva, Bruna Karadien
dc.contributor.authorCorrea, Renan Oliveiraen
dc.contributor.authorPereira de Andrade, Mirella Cristinyen
dc.contributor.authorda Fonseca, Denise Moraisen
dc.contributor.authorBasso, Paulo Joseen
dc.contributor.authorSaraiva Camara, Niels Olsenen
dc.contributor.authorde Sales e Souza, Ericka Lorennaen
dc.contributor.authorMartins, Flaviano dos Santosen
dc.contributor.authorSato Guima, Suzana Eikoen
dc.contributor.authorThomas, Andrew M.en
dc.contributor.authorSetubal, Joao Carlosen
dc.contributor.authorMagalhaes, Yuli Thamiresen
dc.contributor.authorForti, Fabio Luisen
dc.contributor.authorCandreva, Thamirisen
dc.contributor.authorRodrigues, Hosana Gomesen
dc.contributor.authorde Jesus, Marcelo Bispoen
dc.contributor.authorConsonni, Silvio Robertoen
dc.contributor.authorFarias, Alessandro dos Santosen
dc.contributor.authorVarga-Weisz, Patricken
dc.contributor.authorRamirez Vinolo, Marco Aurelioen
dc.date.accessioned2019-08-21T19:40:25Zen
dc.date.available2019-08-21T19:40:25Zen
dc.date.issued2019-04-16en
dc.description.abstractAntibiotic-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.en
dc.description.notesThis study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; grants 2012/10653-9, 2013/06810-4, 2014/03002-7, 2015/06134-4, 2017/16280-3, and 2018/01753-6), Funcamp, National Council for Scientific and Technological Development (CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) - Finance Code 001, a Newton Advanced Fellowship by the Royal Society (between M.A.R.V. and P.V.-W.). J.L.F., L.P.P., B.K.S., R.O.C., Y.T.M., and T.C. are recipients of fellowships from FAPESP (2017/06577-9, 2018/02208-1, 2017/25679-7, 2016/23142-3, 2017/01451-7, and 2017/26366-2). A.M.T. was supported by a fellowship from FAPESP (2015/01507-7). We thank Juri Kazakevych for help with the RNA sequencing analyses and Maria Teresa Pedrosa Silva Clerici for the formulation of the diets.en
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/10653-9, 2013/06810-4, 2014/03002-7, 2015/06134-4, 2017/16280-3, 2018/01753-6]; Funcamp; National Council for Scientific and Technological Development (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]; Newton Advanced Fellowship by the Royal Society; FAPESP [2017/06577-9, 2018/02208-1, 2017/25679-7, 2016/23142-3, 2017/01451-7, 2017/26366-2, 2015/01507-7]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2019.03.054en
dc.identifier.issn2211-1247en
dc.identifier.pmid30995474en
dc.identifier.urihttp://hdl.handle.net/10919/93202en
dc.language.isoenen
dc.publisherCell Pressen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.titleButyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanismen
dc.title.serialCell Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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