Molecular Mechanisms of Microbiota Metabolite Action on Intestinal Stem Cells

• Grant number: 24/17623-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Raissa Guimarães Ludwig
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 23/14946-5 - Deciphering the molecular mechanisms of soluble fibers, in the host and microbiota, during intestinal inflammatory and regenerative responses, AP.TEM

Abstract

The intestinal microbiota plays a fundamental role in regulating metabolic and immunological processes and in maintaining the intestinal barrier. Diet, especially with soluble fibers such as inulin, modulates the composition and functionality of the microbiota. Studies show that inulin intake stimulates the proliferation of stem cells and the remodeling of the intestinal epithelium. Given that the composition of the microbiota is fundamental to this phenotype, we hypothesize that the metabolites produced by intestinal bacteria act as the main mediators of the effects promoted by inulin, altering important metabolic pathways for the proliferation of intestinal epithelial cells. The present study aims to investigate the mechanisms by which bacterial metabolites produced by inulin intake alter the proliferation of intestinal stem cells. In vitro experiments will involve using Caco-2 cells, a human colon lineage, for functional analysis in the presence of metabolites from the processing of inulin by the microbiota, followed by CRISPR-Cas9 screening to identify genes involved in cell proliferation. In vivo experiments will be conducted to evaluate the impact of the inulin diet on intestinal proliferation in mice genetically modified for the HCAR2 gene in intestinal epithelial cells for the gene. The results of this study will contribute to the understanding of the molecular mechanisms associated with the action of inulin, offering new insights into how this fiber can be used more effectively in clinical interventions. (AU)