Defining the mechanistic link between Akkermansia muciniphila and gut microbiome metabolites in the pathogenesis of cardiovascular disease
Supervisors:
Dr Qiaozhu Su, School of Biological Sciences and Institute for Global Food Security (Queen's University Belfast)
Dr Dónal Wall, School of Infection and Immunity (University of Glasgow)
Summary:
Dysbiosis of gut bacteria plays an important role in the onset of cardiovascular disease (CVD). In humans, increased circulating gut bacterial metabolite Trimethylamine N-oxide (TMAO) is closely associated with high risk of CVD. The overarching goal of this project is to investigate the protective mechanism of A. muciniphila on CVD caused by increased B. theta, and its effects on increased gut microbiome-derived trimethylamine metabolites induced by a high-fat diet containing high milk saturated fat.
The proposed work pursues three specific Aims.
(i) Define the anti-inflammatory mechanism of A. muciniphila against high-fat-diet induced CVD in an apolipoprotein E knockout mouse model by suppressing the growth of B. theta and inhibiting cardiac inflammatory response;
(ii) Explore the pathophysiological mechanism of A. muciniphila on alleviating inflammatory stress in cardiomyocytes and vascular endothelial cells by suppressing the TMA and TMAO metabolic pathways;
(iii) Determine the cardiac protective effect of A. muciniphila on preventing accumulation of the novel trimethylamines in the heart and the subsequent induction of oxidative stress.
Research outcomes from this project will provide novel insight into the pathophysiological conditions of myocarditis and atherosclerosis, which may lend support to develop therapeutic strategy for CVD by manipulating food consumption and gut microbiome populations.
Successful completion of this PhD training program will equip the graduate with the necessary skills to enter the job market, drive progress in biomedical science and tackle global challenges in sustainability.