The gut and bias benefits - the investigation on urolithin metabotypes. Producer strains isolation and multiomic-based description of ellagitannin biotransformation.

Project Information

UroAPROD

Grant agreement ID: 101106272

DOI

10.3030/101106272

Project closed

EC signature date 12 April 2023

Start date 1 February 2024

End date 28 February 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 191 760,00

Coordinated by

UNIVERSITEIT ANTWERPEN
Belgium

Periodic Reporting for period 1 - UroAPROD (The gut and bias benefits - the investigation on urolithin metabotypes. Producer strains isolation and multiomic-based description of ellagitannin biotransformation.)

Reporting period: 2024-02-01 to 2026-02-28

Summary of the context and overall objectives of the project

The human gut microbiome plays a crucial role in transforming dietary compounds into bioactive metabolites that can influence health. One important example is the conversion of ellagitannins—polyphenols found in foods such as pomegranates and walnuts—into urolithins, a class of metabolites associated with beneficial effects on metabolism, inflammation, and muscle function. However, not all individuals have urolithins produced, and the underlying microbial mechanisms remain poorly understood.
This project aimed to better understand how gut microorganisms transform dietary polyphenols and why individuals differ in their capacity to produce bioactive metabolites. A key objective was to identify microbial processes and factors influencing urolithin production, including the role of external perturbations such as antimicrobial agents. The project also sought to develop and apply advanced analytical and data-driven approaches to link microbial composition with metabolic outputs.
The work addresses important societal and scientific challenges aligned with European priorities in health, nutrition, and microbiome research. By improving our understanding of diet–microbiome interactions, the project contributes to the development of personalised nutrition strategies and supports innovation in functional foods and preventive healthcare. It also provides knowledge relevant for assessing unintended effects of antimicrobial exposure on beneficial microbial functions.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project combined dietary intervention, ex vivo microbiome experiments, and advanced metabolomics and sequencing approaches. Human volunteers consumed ellagitannin-rich foods, and biological samples were collected to characterise individual differences in urolithin production capacity (metabotypes).
To investigate microbial processes in detail, ex vivo incubations of human gut microbiota were performed using ellagic acid as a model substrate. These experiments were conducted across multiple time points, enabling the monitoring of dynamic metabolic transformations. In parallel, the impact of commonly used antimicrobial agents on these processes was evaluated.
The project generated a large-scale dataset, including thousands of high-resolution mass spectrometry measurements and microbiome profiles. New analytical workflows were implemented, such as computational approaches for prioritising biologically relevant metabolites in complex time-series data.
The main achievements include:
1. Characterisation of inter-individual variability in urolithin production.
2. Demonstration that antimicrobial agents can significantly inhibit the microbial transformation of ellagitannins.
3. Generation of time-resolved metabolomic datasets capturing intermediate and final products of microbial metabolism.
4. Development of data analysis strategies to improve the detection of microbiome-derived metabolites.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project advances the current state of the art by providing a dynamic and integrative view of microbiome-driven metabolism. Unlike previous studies focusing on end-point measurements, this work captures the temporal progression of metabolic transformations, revealing intermediate compounds and pathways that were previously underexplored.
A key novel finding is the sensitivity of beneficial microbial metabolic functions to antimicrobial exposure. This highlights a potential consequence of antibiotic use and underscores the importance of preserving microbiome functionality.
The methodological advances, including improved mass spectrometry workflows and data analysis pipelines, provide tools that can be applied broadly in microbiome and metabolomics research. These approaches facilitate the identification of functional links between microbial communities and metabolic outputs.
The results create opportunities for further research and innovation, including:
1. Identification of microbial taxa responsible for beneficial metabolite production.
2. Development of targeted dietary or probiotic interventions to enhance urolithin production.
3. Integration of metabolomics and microbiome data for personalised nutrition applications.
Further work will be needed to validate findings in larger populations, translate results into clinical or nutritional applications, and explore regulatory and commercial pathways for microbiome-based innovations.

Methodology of ex vivo incubations of gut microbiota and sample analysis

Dietary intervention and metabotype assignment