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Deciphering host-gut microbiota spatio-functional plasticity in inflammation

Project description

Host-gut bacteria feedback interactions during inflammation

Gut microbiota has been emerging as a critical regulator of health. Crohn’s disease (CD) highlights the importance of spatial organisation of microbiota when patches of gut inflammation are surrounded by uninflamed regions in the same host. Previous studies point to host-microbe functional feedback in the bacterial adaptation of immunomodulatory functions, including alterations in gut bacteria of CD patients. The EU-funded ExtractABact project proposes to study bacterial spatio-functional plasticity and host-microbe interactions in CD, affecting inflammation. The combination of microbiology, immunology, and systems biology approaches will allow an understanding of bacterial functional plasticity during inflammation, mechanisms of feedback, and potential role in the initiation of gut inflammation.

Objective

Over the past two decades, gut bacteria have emerged as major regulators of human health. The focus in the field thus far has been on bacterial taxonomy, with their spatial organization and functionality largely overlooked. Crohn’s disease (CD) vividly portrays this spatiofunctional dimension, as it features patches of gut inflammation (skip lesions) surrounded by uninflamed regions—in the same host—with a clear demarcation but unknown cause. Our preliminary data demonstrate host-microbe functional feedback loops in which bacterial strains can adapt and modify their immunomodulatory functions in response to the host. Moreover, we find functional alterations in gut bacteria of IBD patients. Thus, we hypothesize that bacterial spatio-functionality can be largely affected by host physiology, and, in turn, modulate the pathophysiological state, creating a functional feedback loop.
We propose to study bacterial spatiofunctional plasticity and mechanisms of host-microbe interactions in CD, and their potential causal effects on inflammation, combining microbiology, immunology and systems biology approaches. We intend to focus on three independent yet complementary aims: (1) Characterize host-microbe spatio-functional alterations in skip lesions and assess their potential causal effects on inflammation; (2) Decipher the functional and molecular mechanisms of host-microbe feedback loops in healthy and inflamed intestines; and (3) Develop a toolbox for high-resolution functional analyses of gut bacteria directly in their natural environments.
This study will address, for the first time, bacterial functional plasticity in response to host inflammation, unveiling the phenomena, its mechanism of action, and potential causal effects on gut inflammation. Such understanding can shift our perception on microbiota-host interactions, may explain contradictions in the field, point to novel contributing factors to CD and related disorders, and guide future translational studies.

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Call for proposal

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(opens in new window) ERC-2022-STG

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Host institution

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
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.

€ 1 997 500,00
Address
SENATE BUILDING TECHNION CITY
32000 Haifa
Israel

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Activity type
Higher or Secondary Education Establishments
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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.

€ 1 997 500,00

Beneficiaries (1)

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