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

ended

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.