Deciphering the molecular mechanisms of soluble fibers, in the host and microbiota, during intestinal inflammatory and regenerative responses

• Grant number: 23/14946-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2025
• End date: February 28, 2030
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Marco Aurélio Ramirez Vinolo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Andrei Carvalho Sposito ; Carlos Henrique Grossi Sponton ; Daniel Martins-de-Souza ; Eric C Martens ; Helder Takashi Imoto Nakaya ; Hosana Gomes Rodrigues ; Jarlei Fiamoncini ; Mariana Xavier Byndloss ; Patrick Daniel Varga-Weisz ; Vinicius de Andrade Oliveira

Abstract

Dietary fibers act directly on the crosstalk between components of the microbiota, immune system and intestinal epithelial cells. Its intake is generally associated with metabolic and immunological benefits for the host. Despite advances in the area, there are still a limited number of microbial molecules and their possible targets described in the literature. Furthermore, there is a lack of information regarding how differences in the composition of the microbiota between individuals impact these interactions. In this project our main aims are: 1) characterize the mechanisms involved in the effects of inulin during intestinal inflammation and the epithelial regeneration process, 2) characterize the effects of inulin intake on the human microbiota and 3) define functional microbial components/modules that can be used to predict the effects of dietary fiber intake in humans. To this end, we will use a combination of experimental models of intestinal inflammation and regeneration, gain and loss of function experiments, analysis of host components through total and single cell RNA sequencing and immunophenotyping. In the context of microbiota, we will focus on metabolomic and metagenomic analyses. We will perform a controlled and randomized clinical study with fibers, whose objective will be to characterize the taxonomic and functional responses of the human microbiota and their effects on the intestinal epithelium. Finally, we will identify components that allow us to predict responses after ingesting inulin in humans. With this project we will describe new connections between the microbiota and host cells, which will contribute to the development of biomarkers and therapeutic targets for inflammatory diseases. Furthermore, we will identify factors that will allow the use of personalized and more efficient approaches with regard to dietary fiber supplementation. (AU)