| Literature DB >> 30995474 |
José Luís Fachi1, Jaqueline de Souza Felipe1, Laís Passariello Pral1, Bruna Karadi da Silva1, Renan Oliveira Corrêa1, Mirella Cristiny Pereira de Andrade1, Denise Morais da Fonseca2, Paulo José Basso2, Niels Olsen Saraiva Câmara2, Éricka Lorenna de Sales E Souza3, Flaviano Dos Santos Martins3, Suzana Eiko Sato Guima4, Andrew Maltez Thomas4, João Carlos Setubal5, Yuli Thamires Magalhães4, Fábio Luis Forti4, Thamiris Candreva6, Hosana Gomes Rodrigues6, Marcelo Bispo de Jesus7, Sílvio Roberto Consonni8, Alessandro Dos Santos Farias9, Patrick Varga-Weisz10, Marco Aurélio Ramirez Vinolo11.
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.Entities:
Keywords: colitis; hypoxia; infection; intestinal epithelial cells; microbiota; short chain fatty acids
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Year: 2019 PMID： 30995474 DOI： 10.1016/j.celrep.2019.03.054
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423