MicrobiomE-associaTEd boosters Of immune Responses (METEOR study): experimental charac-terization and clinical exploitation.

Informations projet

METEOR study

N° de convention de subvention: 101064842

DOI

10.3030/101064842

Projet clôturé

Date de signature de la CE 22 Juin 2022

Date de début 1 Septembre 2023

Date de fin 31 Decembre 2025

Financé au titre de

• Marie Skłodowska-Curie Actions (MSCA)

Coût total

Aucune donnée

Contribution de l’UE

€ 192 865,12

Coordonné par

FUNDACION PARA LA INVESTIGACION BIOMEDICA DEL HOSPITAL UNIVERSITARIO RAMON Y CAJAL
Spain

Periodic Reporting for period 1 - METEOR study (MicrobiomE-associaTEd boosters Of immune Responses (METEOR study): experimental charac-terization and clinical exploitation.)

Période du rapport: 2023-09-01 au 2025-12-31

Résumé du contexte et des objectifs généraux du projet

The human microbiome has emerged as a critical component influencing immune responses and disease outcomes, however, its therapeutic potential remains poorly addressed. While the scientific community has established that microbiota exerts unique roles in immune system induction, instruction, and functionality, most current research remains descriptive rather than functionally explorative. The METEOR (MicrobiomE-associaTEd boosters Of immune Responses) project addresses this critical knowledge gap through an innovative approach that combines experimental and multi-omics methodologies with clinical translation. The project's central objective is to identify and characterize MIcrobiome-associated BOosters of Immune responses to Diseases (MIBOIDs) through a comprehensive screening of distinct microbiota compartments: Whole Bacterial Community (WBC), sterile filtrates of microbial suspensions (SFMS). The project's five specific objectives create a systematic pathway from discovery to clinical application: understanding differences between microbiota compartments across extreme disease response cohorts, characterizing functional microbiota profiles through multi-omics integration, demonstrating direct host-microbiota interactions through in vitro systems, integrating clinical and experimental data through advanced bioinformatics, and establishing robust protocols for MIBOID production suitable for future clinical exploitation.
The project's potential to generate "know-how" patents and therapeutic agents represents significant economic impact, potentially revolutionizing treatment cost-effectiveness while improving patient health outcomes.
METEOR's comprehensive approach to protocol standardization and open science practices ensures that its methodological innovations will benefit the broader scientific community, and is expected to inspire follow-up studies and leverage additional investment in research and innovation, ultimately contributing to the development of a new class of microbiome-based therapeutic interventions.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

I have established a collection of WBC and SFMS from two unique cohorts: HIV exceptional controllers and extreme immunotherapy responders in lung cancer. This collection represents a valuable resource for investigating the role of microbiome components in modulating immune responses in these clinically significant populations.
Further characterization of this collection using advanced omic technologies is currently in progress. These analyses will provide deeper insights into the taxonomic composition and functional profiles of these microbiome compartments, enabling the identification of potential MIBOIDs.
I have established the best conditions for performing stimulations of immune cells with WBC and SFMS: appropriate cell numbers and culture conditions, optimal concentrations of microbial stimuli, ideal timing parameters for stimulation experiments, etc. These protocols are essential for reliable assessment of microbiome-immune interactions and will serve as a foundation for future experiments within the METEOR project framework.
I have performed quantitative analyses of changes in immune responses following stimulation with microbiome components using: Enzyme-Linked Immunosorbent Assay (ELISA) for cytokine profiling and flow cytometry for immune cell phenotyping and functional assessment. This provides crucial data on how different microbiome compartments influence immune cell activation, cytokine production, and other functional parameters relevant to disease outcomes.
Working collaboratively with our group's bioinformatics team, I have contributed to implementing robust computational pipelines for omic technologies analyses and data integration. We have first tested and published these methods in the context of a previous project (Diaz-García C, Moreno E. et al, Microbiome, 2024). I have also expanded this knowledge during my academic secondment at Dr. Trine Ballestad Rounge at University of Oslo, where I have helped developing experimental protocols for proteomic analysis and applied a bioinformatic analysis able to analyze and find viral sequences using sequencing data regularly used for bacteria sequencing (Virmake, Einar B et al, preprint, 2025).
The work performed so far has served as a starting point to enhance my knowledge about developing therapeutic agents that can be protected by intellectual property and utilized in clinical contexts. I have attended to a certified course of the Spanish Drug Agency (AEMPS) and the "programa de Formación en Creación y Gestión de Startups de Salud," which is part of the Health Start program of the Community of Madrid and focuses on healthcare startup creation and management. These courses together with the non-academic placement period at Mikrobiomik, a leading biopharmaceutical company specialized in developing biological medicines based on the human microbiome, have allowed me to understand better how could I apply in the future the results of my research.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The METEOR project includes significant advances such as the establishment of standardized protocols for immune cell stimulation with isolated microbiome components that address current limitations in microbiome therapeutic development.
We have demonstrated that we can identify microbiome-derived biomarkers with immediate clinical applicability. We identified two outstanding microbiome-derived components that function as excellent diagnostic markers for anal cancer in People Living With HIV (Serrano-Villar S, et al, Nature Medicine, 2023). In METEOR, we are going even further by providing a reproducible experimental platform.
We have established a unique collection of bacterial communities and their subproducts isolated from clinical samples, and we have characterized some immune responses of these microbiome-derived components on immune cells, through ELISA and Flow cytometry (Figure 2). We will keep working on the identification of the best candidates in each disease context. This, together with our advances in parallel in the bioinformatic pipelines, positions the project to contribute significantly to the field of microbiome-based therapeutics.

Quantification of the immune response changes

Summary of the project