Project

Engineering of an abscisic acid (ABA)-producing probiotic yeast strain to modulate host microbiota, intestinal health and inflammatory diseases

Code
3S012820
Duration
01 November 2020 → 31 October 2024
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Microbiomes
    • Cell signaling
  • Medical and health sciences
    • Pharmacotherapy
    • Gastro-enterology
    • Microbiome
Keywords
inflammatory diseases gut microbiome interactions probiotics Synthetic biology metabolites
 
Project description

Intestinal health is known to be strongly determined by the food ingested and by the microbes which populate the gut. In this project we will focus on the interactions between the plant phytohormone abscisic acid (ABA) and the gut microbiome. ABA has previously been shown to be involved in various immune and inflammatory diseases. However, anti-inflammatory effects need to be studied in more detail before ABA can be applied as a true drug strategy. The overall aim of this project is to engineer an ABA-producing probiotic and to study the impact of ABA on the gut microbiome and disease progression in mouse models of colitis and sepsis. Firstly, the impact of synthetic ABA will be determined in our disease models. Secondly, an ABA-producing probiotic Saccharomyces boulardii yeast strain will be engineered and we will evaluate the phenotypic effects of its administration in our disease models, as well as investigate in more detail the effects on the composition of the gut microbiome. Additionally, to rule out the influences of endogenous ABA, we have previously developed transgenic ABA-depleted mice. We will compare our observations in wild type mice with observations made in transgenic mice. Lastly, by comparing observations in the specific pathogen free (SPF) mice with more “clean” germ-free mice and more “dirty”, natural microbiome “wildling” mice, we will check whether the protective effects of ABA in our disease models are dependent on environmental conditions.