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Investigating the Impact of Inulin Metabolites on G-Protein Coupled Receptors Activation.

Grant number: 23/12527-5
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): January 01, 2024
Effective date (End): December 31, 2024
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Marco Aurélio Ramirez Vinolo
Grantee:Laís Passariello Pral
Supervisor: Noah Wolcott Palm
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: Yale School of Medicine (YSM), United States  
Associated to the scholarship:20/13689-0 - The role of histone crotonylation in intestinal stem cells, BP.DR

Abstract

Inulin, a non-digestible fiber, is fermented by gut bacteria that produce different metabolites including short-chain fatty acids (SCFAs), lactate, inositol-triphosphate and indoles, which impact on host's cells functions. While there is a lot of information available regarding the host-modulating effects of the main short-chain fatty acids (acetate, butyrate, and propionate) and their associated G protein-coupled receptors (GPCRs), it's crucial to emphasize that the microbiota produces a wide range of other metabolites with the potential to activate a diverse array of receptors. In a recent work, we demonstrated that the intake of the fiber inulin increases the proliferation of intestinal stem cells in the colon epithelium, an effect that was dependent on the microbiota and immune components, including the ³´ T cells. Despite having observed these effects, we have yet to precisely elucidate the underlying mechanisms. Therefore, the primary objective of this project is to explore whether GPCR ligands produced through microbial fermentation of the inulin diet, including crotonate and many other, play a significant role in host cells. For that purpose, we will isolate, profile and culture microbiota from inulin treated mice, and obtain the metabolites produced by the microbial populations. We then will proceed to perform a multiplexed screening protocol - the PRESTO-Salsa method-, with which we will be able to define which microbiota inulin-derived compounds are able to trigger specific GPCRs activation, and their consequences to cellular functions. With these findings, we intend to further extend the current knowledge on how dietary compounds influence the host microbiota, and the effects of this interaction to the host's cell functions.((

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