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Microbial therapy against gut inflammation

Project description

Hijacking bacterial mechanisms to restore gut microbiota composition

Bacteria have an inherent capacity to regulate gene expression based on fluctuations in cell density, an attribute known as quorum sensing (QS). Emerging evidence indicates that gut microbiota employ different pathways of QS to communicate with each other for spatial dominance. Scientists of the EU-funded MAGI project propose to exploit QS to address the imbalanced microbiota (dysbiosis) observed in inflammatory bowel disease. The idea is that manipulation of QS will alleviate the impact of antibiotics and restore gut microbiota composition and hence function. Given the central role of microbiota in the metabolic or immune status of the host, a QS-based intervention may have additional benefits.

Objective

Gut microbiota support intestinal tract development, immune system maturation, and protection against pathogens. Imbalanced microbiota (dysbiosis) has a role in inflammatory bowel disease (IBD). To control inflammation, patients take antibiotics, exacerbating dysbiosis, leading to loss of colonization resistance against pathogens and proliferation of pathobionts, disease development and progression. Microbiota composition has, therefore, a very important role in host health, and strategies to manipulate this composition are lacking. Microbiota-produced molecules, like quorum sensing (QS) signal autoinducer-2, can influence gut composition. Bacteria use QS to regulate populational gene expression. We intend to take advantage of microbial interactions mediated by QS to tackle IBD dysbiosis. We will design biotherapies to attenuate the detrimental dysbiotic effects on host health, focusing on gut QS in IBD. The microbiota imbalance observed in IBD leads to high inflammation, expansion of pathobionts, and loss of protection against infections. In previous work, we have shown that by committing the gut microbiota to inter-species QS we could increase members of the microbiota affected by antibiotics, highlighting the potential of QS manipulation to counteract dysbiosis. We propose to manipulate QS of native gut microbes to counteract IBD-associated dysbiosis, and thus inflammation and loss of protection associated with it, rescuing normal microbiota functions. We will tackle dysbiosis by manipulating QS signalling and by fostering specific beneficial interactions amongst microbes. The potential of this therapy, as an alternative or complement to antibiotics, is centred on bypassing the worsening of dysbiosis, like loss of protection against the expansion of inflammation-driving pathobionts and infections, as well as the attenuation of inflammation.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-RI - RI – Reintegration panel

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

FUNDACAO CALOUSTE GULBENKIAN
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.

€ 147 815,04
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.

€ 147 815,04
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