Role of the epigenetic changes induced by SCFAs in intestinal epithelial cells

• Grant number: 15/14105-4
• Support type: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): October 01, 2015
• Effective date (End): March 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Renan Oliveira Corrêa
• Supervisor abroad: Patrick Daniel Varga-Weisz
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Local de pesquisa : Babraham Institute, England
• Associated to the scholarship: 14/02560-6 - Role of short chain fatty acids and their receptor (GPR43) in the immune response against Aggregatibacter actinomycetemcomitans in a mono-infection model, BP.MS

Abstract

Short chain fatty acids (SCFAs, mainly acetate, propionate, and butyrate) are bacterial metabolites produced during fermentation of dietary fibers in the intestinal tract. These nutrients modulate the production of inflammatory mediators including chemokines, cytokines, and antimicrobial peptides by intestinal epithelial cells. In the present project, we aim to establish an in vitro model (culture of murine intestinal organoids) in order to investigate epigenetic modifications caused by SCFAs and the influence of that in the expression of inflammatory genes. For that, murine intestinal organoids will be incubated in four different conditions: 1) with no SCFAs (control group); 2) with a mix of SCFAs at low concentration (6 mM acetate; 1 mM propionate and 1 mM butyrate) simulating the intestinal profile of animals treated with antibiotics; 3) with a mix of SCFAs at a concentration normally found in the gut of animals (50 mM acetate; 10 mM propionate and 10 mM butyrate); and 4) with a mix of SCFAs at high concentration (59 mM acetate; 19 mM propionate and 17 mM butyrate) simulating the intestinal profile of animals with high intake of dietary fibers. We will analyze growth and viability of organoids incubated in the conditions described above. Additionally, we will perform transcriptome analysis (mRNA expression, mRNA-seq) to determine the profile of gene activation/deactivation and epigenetic modifications analyzes by chromatin immuno-precipitation (ChIP) and western blot. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FELLOWS, RACHEL; DENIZOT, JEREMY; STELLATO, CLAUDIA; CUOMO, ALESSANDRO; JAIN, PAYAL; STOYANOVA, ELENA; BALAZSI, SZABINA; HAJNADY, ZOLTAN; LIEBERT, ANKE; KAZAKEVYCH, JURI; BLACKBURN, HECTOR; CORREA, RENAN OLIVEIRA; FACHI, JOSE LUIS; SATO, FABIO TAKEO; RIBEIRO, WILLIAN R.; FERREIRA, CAROLINE MARCANTONIO; PEREE, HELENE; SPAGNUOLO, MARIANGELA; MATTIUZ, RAPHAEL; MATOLCSI, CSABA; GUEDES, JOANA; CLARK, JONATHAN; VELDHOEN, MARC; BONALDI, TIZIANA; RAMIREZ VINOLO, MARCO AURELIO; VARGA-WEISZ, PATRICK. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. NATURE COMMUNICATIONS, v. 9, JAN 9 2018. Web of Science Citations: 59.