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At the host-bacteria interface: Modulation of the intestinal microbiota and its metabolic activity by Card9 signalling in health and Inflammatory Bowel Diseases

Objective

The microbial community in the human intestine is crucial to the health and nutrition of the host. Loss of the fragile balance within this complex ecosystem is involved in numerous pathologies, including inflammatory bowel disease (IBD). The incidence of IBD is increasing and affects individuals in challenging years of their lives, with immunosuppressive treatments that are not always effective.
IBD results from a combination of genetic predisposition, alteration of the gut microbiota, and environmental influences. Thus, deciphering the host-bacteria crosstalk will improve our understanding of IBD and enable new preventive and therapeutic strategies. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, codes for a protein involved in the response to fungi and bacteria. Sokol and colleagues showed that Card9-/- mice have an increased susceptibility to colitis, due to an altered gut microbiota that is not able to metabolise tryptophan into aryl hydrocarbon receptor (AhR) ligands. In humans, comparable mechanisms seem to be involved, as microbiota of IBD patients exhibit impaired production of AhR ligands, which mirrors the Card9-/- genotype.
We aim to decipher the mechanisms involved in the modulation of the microbiota and its metabolic activity by Card9. For this purpose, we will take advantage of a strong collaborative environment and cutting-edge techniques, including gnotobiotic animals, cre-lox technology, transcriptomics, metabolomics and systems biology. Specifically, we plan to identify (i) new pathways and cell types involved in the modulation of the microbiota and its metabolic activity, and (ii) microorganisms and metabolites activating AhR receptors in the gut.
This highly innovative and integrative project will allow me to expand my conceptual and technical knowledge of the gut-microbiota interface, acquire new key skills and strengthen my scientific network.

Fields of science (EuroSciVoc)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2016

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Coordinator

INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT
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.

€ 185 076,00
Address
147 RUE DE L'UNIVERSITE
75007 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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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.

€ 185 076,00
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