Atherosclerotic cardiovascular disease is the worldwide leading cause of death. Identification and interventions against modifiable cardiovascular risk factors have contributed to a stark reduction in the incidence. However, the proportion of patients with myocardial infarction and stroke without known risk factors is increasing and accounts for 15–30% of patients in studies from Australia and Sweden. We now need to identify the remaining underlying causal risk factors to be able to provide new effective preventive strategies. Atherosclerotic plaque starts forming already in childhood on the inside of artery walls by a build-up of lipids, fibrous elements, calcium, and inflammatory molecules. With age, plaques that are prone to rupture become more common. When a plaque ruptures, it exposes its inner parts to the blood flow, leading to blood clot formation and potentially to myocardial infarction or stroke. The mechanisms driving atherosclerosis formation and progression are partly unknown, and the theory of a microbial contribution was proposed at the beginning of the last century. Even in a healthy state, humans carry a large number of commensal microbes on all mucosal surfaces - the microbiome - that could play a role in atherogenesis. The overall aim of this project was to identify gut bacterial species or products that accelerates or hampers the development of atherosclerotic disease and to provide easily accessible blood biomarkers for an atherosclerosis-enhancing gut microbiota. The field of microbiota research is of great attention, but the field lacks smart study designs that assess true causal effects of gut dysbiosis. Our research is anticipated to lead to identification of atherosclerosis-enhancing gut microbiota characteristics and their associated biomarkers that may open up new avenues for effective population-wide long-term prevention of atherosclerotic disease.
