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Evolution in the Gut in Health and Disease

Project description

Insight into gut microbiome evolution

The gut microbiome is a complex community of trillions of microorganisms, including bacteria, viruses and fungi, that live in the digestive tract and play a crucial role in digestion, immunity and overall health. Understanding how microbiome diversity evolves is central to maintaining host health. The ERC-funded EvoInHi project will use the gut microbiome as a model system to study microbial ecology and uncover the role of natural selection in health and disease. The work will focus on Escherichia coli and explore the impact of resource competition in microbial selection in healthy guts and how this is altered under environmental fluctuations.

Objective

The mammalian gut is an exquisite system to study ecology and evolution of microbes, and these processes are key for host-microbiome homeostasis. How microbiome diversity is maintained or lost is a critical question underlying the proper balance of this duet. Yet, our knowledge of the eco-evolutionary mechanisms structuring microbiomes is still in its infancy. Here, we seek to identify dominant modes of natural selection and host factors that modulate the evolution of their microbes. By leveraging knowledge on gene functions in specific strains and the power of mouse genetics and husbandry, we will unravel how natural selection operates to shape diversity in the bacteria that inhabit the guts of healthy and sick hosts.
Microbiome evolution will be studied in several mouse models of disease with a focus on Escherichia coli as a pathobiont model, for which a deeper understanding of molecular mechanisms in health vs disease can be reached. Using long-term experimental evolution in vivo, high-throughput sequencing and theoretical modelling we will quantify the relative roles of directional, diversifying and fluctuating selection in gut evolution. We posit that resource competition drives the dominant selection mode in the healthy gut and that strong fluctuations in the environment, due to phage-bacteria co-evolution and/or due to hostmicrobe interactions, drive the selection mode in the gut of diseased hosts.
We will further test the hypothesis that fluctuating selection leads to an Anna Karenina effect whereby the microbiomes of unhealthy individuals are much more distinct between one another than those of heathy ones. EvoInHi seeks to find the first empirical evidence that the predictability of evolution is higher in health than in disease, which will have a profound impact on understanding bacteria diversity and rates of specialization and how these can be used to modulate host health.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-ADG

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Host institution

FUNDACAO GIMM - GULBENKIAN INSTITUTE FOR MOLECULAR MEDICINE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 949 537,00
Address
AVENIDA PROFESSOR EGAS MONIZ
1649-035 LISBOA
Portugal

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 949 537,00

Beneficiaries (3)

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