Cell Reports
| Autor: | Renan O. Corrêa, Laís Passariello Pral, Andrew Maltez Thomas, Yuli Thamires Magalhães, Niels Olsen Saraiva Câmara, Marcelo Bispo de Jesus, Mirella Cristiny Pereira de Andrade, Jaqueline de Souza Felipe, Éricka Lorenna de Sales e Souza, José Luís Fachi, Marco Aurélio Ramirez Vinolo, Suzana Eiko Sato Guima, Bruna Karadi da Silva, Alessandro S. Farias, Sílvio Roberto Consonni, Paulo José Basso, Hosana G. Rodrigues, Denise Morais da Fonseca, João C. Setubal, Fabio Luis Forti, Patrick Varga-Weisz, Flaviano S. Martins, Thamiris Candreva |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Administration Oral Butyrate General Biochemistry Genetics and Molecular Biology Permeability Microbiology Tight Junctions 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans Insulin Colitis Intestinal Mucosa Transcription factor lcsh:QH301-705.5 Barrier function Triglycerides Toxins Biological Tight junction Chemistry Clostridioides difficile Microbiota Epithelial Cells Clostridium difficile medicine.disease Fatty Acids Volatile ANTIBIÓTICOS Epithelium Anti-Bacterial Agents Mice Inbred C57BL Butyrates 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Hypoxia-Inducible Factor 1 Dysbiosis 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Cell Reports, Vol 27, Iss 3, Pp 750-761.e7 (2019) |
| Popis: | 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. Fundacao 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] This 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|