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Evolution in the Gut in Health and Disease

Descripción del proyecto

Nuevos conocimientos sobre la evolución del microbioma intestinal

El microbioma intestinal es una compleja comunidad de billones de microorganismos, entre los que se incluyen bacterias, virus y hongos, que viven en el tubo digestivo y desempeñan un papel fundamental en la digestión, la inmunidad y la salud en general. Comprender la evolución de la diversidad del microbioma es esencial para mantener la salud del hospedador. En el proyecto EvoInHi, financiado por el Consejo Europeo de Investigación, se empleará el microbioma intestinal como sistema modelo para estudiar la ecología microbiana y dilucidar el papel de la selección natural en la salud y la enfermedad. La investigación se centrará en «Escherichia coli» y se examinará el efecto de la competencia por recursos en la selección microbiana en intestinos sanos y cómo se altera en caso de fluctuaciones ambientales.

Objetivo

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.

Ámbito científico (EuroSciVoc)

CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.

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Régimen de financiación

HORIZON-ERC - HORIZON ERC Grants

Institución de acogida

FUNDACAO CALOUSTE GULBENKIAN
Aportación neta de la UEn
€ 2 096 250,00
Coste total
€ 2 096 250,00

Beneficiarios (2)