Project Details
Projekt
The role of immunomodulation by microbiota and metabolomics in the pathogenesis of atherosclerosis and in cardiovascular risk assessment
Subject Area
Cardiology, Angiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 451892213
Human microbiome affects health by different, often unrevealed pathways. Oral cavity hosts a number of bacterial species that may cause periodontal disease but also promote other common diseases (ischemic heart disease - IHD, arthritis etc.). Intestines contain the largest ecosystem of bacteria. In both these places one finds sites of immune cells proliferation, maturation and exposure to antigens. The exposure of immune cells to microbial organisms and their products may modulate the inflammatory response and promote low grade inflammation. The hypothesis to be verified in this study is that particular compositions of oral or intestinal microbiome may influence the immune cells by low molecular substances. This mechanism may involve methylation of the DNA and hence alter expression of inflammatory mediators by leukocytes. The premise is that it creates chronic low-grade inflammation promoting atherosclerosis.The project will use a deeply phenotyped population-based study to reveal novel “-omics” markers (microbiome, metabolome, DNA methylation patterns and inflammatory mediators) associated with subclinical atherosclerosis and related inflammatory processes leading to manifest atherosclerosis.Complementary, these “-omics” as well as multiple clinical variables of this cohort will be used to predict the change of atherosclerosis-related markers as well as the incidence of manifest atherosclerosis and its outcomes in a followed-up period of five years.The initial results will provide insight into the composition of the microbiome, and which metabolites patterns predispose the development of preatherosclerotic changes (endothelial dysfunction, intima media thickness, retinal vessel abnormalities) and atheroma (in carotids or presenting as symptoms of IHD or stroke). Based on our study we will chose the most probable metabolites and the most likely metabolomic biomarkers that may predispose for the atherosclerosis and test their effects on methylation patterns and gene expression levels of blood cells. This information will be integrated developing an algorithm to evaluate the risk of atherosclerosis based on the combination of novel “-omics” biomarkers with widely accepted clinical information. It may improve the identification of individuals at highest risk of e.g. IHD and thus allowing earlier intervention decreasing morbidity and mortality.
DFG Programme
Research Grants
Cooperation Partners
Professor Dr. Marcus Dörr; Professor Dr. Markus M. Lerch; Professor Dr. Matthias Nauck; Professor Dr. Uwe Völker
