SUPR
multi-omics analysis to explore Interaction between gut microbiota and the intestinal mucosal barrier
Dnr:

NAISS 2023/23-618

Type:

NAISS Small Storage

Principal Investigator:

Vishnu Prasoodanan

Affiliation:

UmeƄ universitet

Start Date:

2023-12-22

End Date:

2025-01-01

Primary Classification:

10605: Immunology (medical to be 30110 and agricultural to be 40302)

Webpage:

Allocation

Abstract

The intestinal mucosal barrier serves as the primary interface between the host and the gut microbiota and is therefore crucial in maintaining a balance that allows for tolerance of commensal bacteria while simultaneously protecting against intestinal pathogens. Moreover, keeping the commensal bacteria at a distance from the host prevents infections and inflammation. As a first line of defense, the intestinal epithelium is covered with a dense layer of mucus that serves as a physical barrier against microbial threats. Among various factors, the microbiota plays a crucial role in influencing the mucus barrier, but the molecular details of this interaction are not yet known. Diet is one of the most important factors that modulate the microbiota composition in the gut. In this project, we try to better understand the interaction between diet, gut microbiome and mucosal barrier function. Therefore, we implemented dietary interventions in mouse models (with transplanted human gut microbiome) by offering a high-fiber diet as well as a Western-style diet, and subsequently measured mucus function on viable tissue. Afterwards, we sequenced the gut microbiota by 16S amplicon sequencing, whole metagenome shot-gun sequencing, we analyze host tissue transcription by RNAseq analyses, and we performed metabolomics of the intestinal content to identify microbial molecules that signal to the host and may be crucial for mucus function. Analysis of the above-mentioned data aims to provide a comprehensive understanding of the intricate relationship between the gut microbiota and the mucus barrier. Specifically, the investigation seeks to uncover the influence of commensal gut bacteria on mucus function and the significance of microbial metabolites in maintaining optimal mucus functionality. Moreover, the study endeavors to elucidate the host pathways responsible for sensing these microbial signals and contributing to the growth of the mucus layer. Additionally, the research explores the potential for modulating the interaction between the microbiota and the host by introducing dietary fiber substrates.