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Human gut Microbiome, gene Expression and Colorectal Cancer: Assigning causal roles from a novel Mendelian randomization perspective.

Objective

The contribution of the gut microbial ecosystem to colorectal cancer (CRC) is not well understood. Inflammatory processes and unbalance cell proliferation in the host could be behind observed correlations between a microbe and cancer stages. However, the enrichment of a microbe at a tumour site does not directly assume causation. Rather, this could be the result of a reverse causation or a confounding third factor. Therefore, two major challenges unravelling CRC aetiology are (i) to identify the mechanistic interactions of microbial communities with host intestinal epithelium cells, and (ii) to assign causality to carcinogenesis. These are the aims of this project integrating different “omic” data, and using a Mendelian randomization (MR) approach.
In this study we analyse microbiome sequencing data, from up to 500 normal colon mucosa biopsies, to provide a comprehensive description of the gut microbiome. Additionally, we integrate transcriptomic data from these well phenotyped 500 samples to understand the interaction between microbes and the gut epithelial cells. Finally, using the germ-line genetic variation of host cells as a third “omic” layer, the correlations between microbes and (i) environmental exposures, (ii) gene expression, and (iii) CRC can be validated by MR. MR is an analytical approach whereby germ-line genetic markers are used as proxies – or instrumental variables – for putative risk factors. These genetic markers cannot be influenced by reverse causation, and, assuming an absence of pleiotropy, can provide unconfounded estimates of association. Therefore, a MR association between genetic proxies and the outcome of interest would indicate that the exposure being proxied is associated in a causal manner.
The identification of the functional relevance and key mediators of gut microbiome to colorectal cancer development is going to increase the development of therapeutic approaches and prevention strategies.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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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-2017

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Coordinator

FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE
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.

€ 158 121,60
Address
AVENIDA GRAN VIA HOSPITALET 199-203
08908 L'Hospitalet De Llobregat
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
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.

€ 158 121,60
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