Proteome-wide Functional Interrogation and Modulation of Gut Microbiome Species

Project Information

ProFITGut

Grant agreement ID: 101076015

DOI

10.3030/101076015

EC signature date 16 December 2022

Start date 1 May 2023

End date 30 April 2028

Funded under

• European Research Council (ERC)

Total cost

€ 1 499 980,00

EU contribution

€ 1 499 980,00

Coordinated by

UMEA UNIVERSITET
Sweden

Periodic Reporting for period 1 - ProFITGut (Proteome-wide Functional Interrogation and Modulation of Gut Microbiome Species)

Reporting period: 2023-05-01 to 2025-10-31

Summary of the context and overall objectives of the project

The community of microorganisms that live in our digestive tract (our gut microbiome) is crucial in maintaining health and influencing disease. While there are multiple studies linking imbalances in this ecosystem to various diseases, we still know very little about what the proteins produced by these microbes actually do, and we have no way to modulate their function. This hinders the development of targeted therapies that could manipulate the microbiome towards a healthy state.
The ProFITGut project aims to bridge this knowledge gap by systematically uncovering the functions and interactions of proteins produced by gut microbiome species. The project will use high-throughput proteomics to study the proteome of common and diverse gut bacterial species upon drug treatment. This will lead to suggestions on the function of proteins, as well as, on how drugs affect bacterial growth. Ultimately, this will allow developing strategies to rationally manipulate the gut microbiome by targeting disease-associated species or 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 ProFITGut project is advancing our understanding of the human gut microbiome by investigating the functions of microbial proteins and how they respond to various chemical compounds. This work is essential for uncovering how gut bacteria interact with each other, with their host, and with commonly used drugs.
Over the reporting period, the project has made substantial progress across all its scientific objectives. A large-scale experimental framework was established to systematically analyze how proteins in diverse gut microbial species respond to a wide range of drugs. This has provided the first steps on how drugs that are not traditionally considered antibiotics can influence microbial growth and metabolism. In parallel, we have started to map how gut microbes resist chemical perturbations, identifying molecular systems that may help bacteria evade the effects of drugs. These insights could inform strategies to mitigate unwanted side effects of medications on the microbiome or to selectively target harmful species. Finally, the project is exploring how microbial species influence each other’s growth and survival, which offers the foundation for future approaches to reshape microbial communities in beneficial ways.

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 is delivering results that significantly advance the current frontiers of microbiome research. While many studies have catalogued the species present in the human gut, ProFITGut goes further by systematically mapping the functional proteome of gut microbes.
One of the project’s most notable breakthroughs is the scale of its proteomic profiling. By analyzing thousands of samples across dozens of microbial species and drug treatments, the project is generating one of the most comprehensive datasets of microbial protein responses to chemical perturbation. This enables the identification of drug mechanisms of action and resistance in gut microbes, including for drugs not traditionally considered antimicrobial. These insights are novel and open new avenues for drug repurposing and microbiome-targeted therapies.
The project also reveals previously uncharacterized interspecies interactions at the molecular level, including both competitive and cooperative relationships. These findings provide a mechanistic basis for understanding how microbial communities assemble and how they might be rationally manipulated to promote health.
At the end of the project, these advances will have the potential to enable precise microbiome modulation, where drugs or interventions are designed to selectively target or support specific microbial functions or species, and improve drug safety and efficacy by identifying unintended microbiome effects of existing pharmaceuticals.