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

Author(s):Show less -

Fachi, Jose Luis ^[1] ; Felipe, Jaqueline de Souza ^[1] ; Pral, Lais Passariello ^[1] ; da Silva, Bruna Karadi ^[1] ; Correa, Renan Oliveira ^[1] ; Pereira de Andrade, Mirella Cristiny ^[1] ; da Fonseca, Denise Morais ^[2] ; Basso, Paulo Jose ^[2] ; Saraiva Camara, Niels Olsen ^[2] ; de Sales e Souza, Ericka Lorenna ^[3] ; Martins, Flaviano dos Santos ^[3] ; Sato Guima, Suzana Eiko ^[4] ; Thomas, Andrew Maltez ^[4] ; Setubal, Joao Carlos ^{[4, 5]} ; Magalhaes, Yuli Thamires ^[4] ; Forti, Fabio Luis ^[4] ; Candreva, Thamiris ^[6] ; Rodrigues, Hosana Gomes ^[6] ; de Jesus, Marcelo Bispo ^[7] ; Consonni, Silvio Roberto ^[8] ; Farias, Alessandro dos Santos ^[9] ; Varga-Weisz, Patrick ^{[10, 11]} ; Ramirez Vinolo, Marco Aurelio ^[1]

Affiliation:Show less -

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Immunoinflammat, BR-13083862 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Fed Minas Gerais, Inst Biol Sci, Dept Microbiol, Lab Biotherapeut Agents, BR-31270901 Belo Horizonte, MG - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo, SP - Brazil

^[5] Virginia Polytech Inst & State Univ, Biocomplex Inst, Blacksburg, VA 24061 - USA

^[6] Univ Estadual Campinas, Sch Appl Sci, Lab Nutrients & Tissue Repair, BR-13484350 Limeira, SP - Brazil

^[7] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Nanocell Interact Lab, BR-13083862 Campinas, SP - Brazil

^[8] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Citochem & Immunocitochem, BR-13083862 Campinas, SP - Brazil

^[9] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Neuroimmunol, BR-13083862 Campinas, SP - Brazil

^[10] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex - England

^[11] Babraham Inst, Nucl Dynam Programme, Cambridge CB22 3AT - England

• Document type: Journal article
• Source: CELL REPORTS; v. 27, n. 3, p. 750+, APR 16 2019.
• Web of Science Citations: 3

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. (AU)

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