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Impact of maternal Adrenomedullin on the Microbiome and Gut health: insights into preventing chronic intestinal disorders

Project description

Maternal milk adrenomedullin as a guardian of gut health

Inflammatory bowel disease (IBD) is an umbrella term for Crohn’s disease and ulcerative colitis, conditions characterised by chronic inflammation of the gastrointestinal tract. Recent studies revealed a protective role of endogenous adrenomedullin (AM), a hormone found in maternal milk, in IBD onset. The EU-funded I-AM-GUT project hypothesises that maternal AM impacts the breast and gut microbiome, immune development and IBD susceptibility. The project's objective is to employ a mammary gland conditional AM knock-out to unravel AM impact on the breast microbiome, on healthy gut development in infancy as well as on the diagnosis and prevention of IBD.

Objective

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal inflammation that has become a global disease with a high economic burden. Adrenomedullin (AM), a hormone associated with gut microbiota and physiology, is naturally present at high concentrations in maternal milk and during lactation. Using a conditional model for AM the fellow identified a protective role of endogenous AM in IBD onset, however relatively little is known about its exact role in early-life, in colitis development or as a potential diagnostic tool for IBD. The fellow hypothesizes that maternal AM’s impact on the breast and gut microbiome may regulate gut and immune development and colitis susceptibility. By creating the first mammary gland conditional knock out for AM, she will uncover novel disease mechanisms and provide the basis for new diagnostic and prevention strategies for IBD. The final goals of this multi-disciplinary project are 1) to unravel the impact of AM on the breast microbiome, the maternal AM influence on healthy infant gut development and the prevention of colitis; 2) to reveal the impact that nutritional intervention and AM administration have on milk and gut microbiome to compensate for dysbiosis and in preventing colitis progression; 3) to evaluate the value of AM as an independent prognostic biomarker for IBD. The project has been carefully designed to match the fellow’s expertise in generating transgenic mice, AM biology and molecular techniques; the expertise of the host institution (APC Microbiome Ireland) in next generation sequencing, cell culture models (organoids), flow cytometry and human studies; and the expertise of the secondment supervisor (UCD) in in situ hybrisation and digital pathology technology. Plans to improve the fellow’s ability to disseminate research findings, gain transferable skills, and learn to manage a project are in place. Ultimately at the end of this fellowship, she will have advanced her position to become an independent researcher.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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

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Coordinator

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
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.

€ 184 590,72
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.

€ 184 590,72
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