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

被引：285

作者：

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
]}

机构：

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

[11] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England

来源：

CELL REPORTS | 2019年 / 27卷 / 03期

基金：

巴西圣保罗研究基金会; 英国生物技术与生命科学研究理事会;

关键词：

CHAIN FATTY-ACIDS; INFLAMMATORY RESPONSES; GUT MICROBIOTA; INFECTION; METABOLITES; BACTERIA; RECEPTOR; DYSBIOSIS; SEQUENCES; DEPLETION;

D O I：

10.1016/j.celrep.2019.03.054

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：750 / +

页数：19

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