Interkingdom Microbial interactions for Translational Innovations (IMiTI)

A scientist examining a petri dish with blue-dotted cultures in a laboratory setting.

Project lead: Anna Júlia Éliás (Semmelweis University)

Participating universities: University of Birmingham, Nantes Université, Semmelweis University

General Overview

The rationale of this project is that the challenging complexity of interactions between the many microorganisms in the gut can only be understood by an interdisciplinary integration of experimental and mathematical models. This understanding is essential for the rational design of effective new probiotics such as strains of yeast that can inhibit the growth of drug-resistant pathogenic bacteria.
The objectives of the experimental part are to develop and validate a sufficiently simple method to analyse the growth of bacterial and fungal co-cultures, in order to find synergistic and antagonistic combinations. The pooling of microbiological resources from Nantes Université and Semmelweis University will make it possible to test different bacterial and fungal species and phenotypes of interest for health.
The objective of the mathematical modelling part is to develop a prototype model of yeast-bacteria interactions in order to use results from pure and mixed cultures in the laboratory to predict interactions in the more complex gut environment and to evaluate combinations of yeast and bacteria for their potential as probiotics. This model will be built by making additions to eGUT, our existing model of bacterial interactions in the gut, to enable the simulation of yeasts.

Purpose and Significance

The microbiota, the microorganisms living within us, have a significant impact on our health. Knowledge of the composition and diversity of the microbiota and the health effects of its members has advanced considerably in recent years. However, the mechanisms that govern polymicrobial interactions remain a challenge for study and discovery. To date, research has focused almost exclusively on the kingdom of bacteria, ignoring the interactions between bacteria and yeasts, which belong to the kingdom of fungi.

Implementation Method and Timeline

This project has four Work Packages (WPs):

  1. Project management: Monitoring the project WPs; securing the approved methodology; ensuring the successful delivery of this interdisciplinary project.
  2. Functional studies of fungi-bacteria interactions: Yeast-bacteria coculture experiments; metabolomic experiments; Sequencing analyses:.
  3. Adding prototype model of yeasts to our eGUT (electronic gut) model and initial verification: Fungi integration to eGUT model; Verification of eGUT model.
  4. Dissemination, knowledge sharing and consortium development: Dissemination of project results through national and/or international scientific conferences and social media; one publication which will be submitted to a high impact academic journal; an online conference to identify collaboration opportunities across EUniWell institutions and beyond.

Expected Outcomes

The following outputs and outcomes are anticipated from this project:

Outcomes:

  • Identification of promising Candida strains that can inhibit multidrug-resistant bacteria.
  • Potential identification of small molecules with therapeutic potential from the human microbiota.
  • Advancements in microbiome analysis through the interdisciplinary combination of experimental and modelling approaches.
  • Consortium building and training opportunities for researchers and students.
  • Creation of grant proposal seeds and teams, which will increase the likelihood of obtaining further funding.

Outputs:

  • Microbiome small molecules and strain candidates for technological developments.
  • Joint publication(s) summarising the findings of the project.
  • Open access enhanced eGUT model.
  • A consortium of gut microbiome researchers across EUniWell with grant seeds ready to go.