Interactions between microbiome, diet metabolite and inflammation in peripheral arterial disease

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis, affecting arteries in the leg. Its symptomatic stages are associated with significant impact in daily life in terms of walking impairment, loss of independence, rest pain or ulcers or gangrene which may lead to amputation. In Sweden, PAD is a growing health issue where it’s prevalence is upto 20% among older people over 60 years of age. This disease leads to an overall decline in quality of life in patients. PAD is associated with increased cardiovascular disease mortality and morbidity and contributes to healthcare costs burden much higher compared to coronary artery disease (CAD). Data from several studies support the role of gut microbiota and dietary consumption of phosphatidylcholine (which is often found in western diet such as meat) in the pathogenesis of atherosclerosis. Production of trymethylamine N-oxide (TMAO) by gut microbiota metabolism of dietary phosphatidylcholine has been associated with the development and progression of atherosclerosis in humans. Despite its high prevalence PAD remains under diagnosed and receives less attention in scientific literature compared to coronary artery disease. Therefore, there is an urgent need for extended research on peripheral arterial disease patients to get better understanding of the disease’s pathophysiology and to define new intervention strategies.

The overall aim of this project is to investigate whether changes in TMAO levels and gut microbiota composition are associated with inflammation in patients with peripheral arterial disease. Using cellular, molecular and physiological approaches developed at the Cardiovascular Research Centre (CVRC), Örebro University and in collaboration with Nutrition-Gut-Brain Interactions Research Centre (NGBI) at Örebro University, Perimed AB, TATAA Biocenter AB, Cellevate AB and Örebro University hospital, we probe how microvascular status, gut microbiota composition, TMAO levels associate with inflammation in peripheral arterial disease patients.  Defining the process in pathophysiology linking gut microbes, TMAO and PAD development could lead to new intervention strategies involving specific dietary and pharmacological approaches to improve health and quality of life in PAD patients.