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Study of the effect of short-chain fatty acids on the tissue regeneration process during experimental colitis

Grant number: 20/02312-3
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Marco Aurélio Ramirez Vinolo
Grantee:Arilson Bernardo dos Santos Pereira Gomes
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation, AP.JP2

Abstract

Colitis is a major Inflammatory Bowel Disease (IBD) and represent an important public health problem. The intestinal microbiota plays an important role in maintaining intestinal homeostasis and contributes to communication with host cells. During epithelial regeneration, Intestinal Stem Cells (ISCs), present in crypts, give rise to precursor cells. It is not yet well understood, how ISCs respond to various signals under pathological conditions. The products of bacterial metabolism, Short-Chain Fatty Acids (SCFA), they are generated during fermentation of non-digestible carbohydrates in the intestine and constitute an important relationship in microbiota-host communication. Studies show that these bioactive agents regulate the host's metabolism and immunity, however, the molecular mechanisms that are involved have not been fully defined. How ISC has relevant participation in the intestinal mucosa and a wide range of interactions with a microbiota, the objective of this project is to assess the role of SCFA and their FFAR2 receptor in the modulation of intestinal epithelial regeneration in the model of colitis induced by 2.5% sodium dextran sulfate (DSS). For this, we will use mice wild-type and knockout for FFAR2, both whole body and tissue-specific, and we will analyze the role of this recptor and the SCFA in the modulation of intestinal epithelial regeneration. In this study, we hope to contribute to the understanding of mechanisms and interaction between host microbiota and identification of a possible therapeutic target. (AU)