Studies on the Bacterial Microbiome in Thrombus Aspirates of Acute Ischemic Stroke Patients

Acute ischemic stroke and other cardiovascular diseases are the major causes of death in the world. For ischemic stroke, traditional risk factors are known, but it seems that they do not completely account for the pattern of epidemiology. Increasing evidence indicates that recent acute infections and chronic infectious diseases are important triggers or risk factors for stroke and other cardiovascular diseases. The role of oral bacteria in the pathogenesis of atherosclerosis and ischemic stroke has gained interest. However, the exact mechanisms of action remain uncertain.

This thesis investigates the role of oral bacteria, especially viridans streptococci, in the etiology of acute ischemic stroke. Viridans streptococci belong to the normal oral microbiome but may cause a severe disease if they enter the systemic circulation, such as in the case of infective endocarditis. In the first study, we studied the presence of bacterial DNA in thrombus aspirates of acute ischemic stroke patients treated with mechanical thrombectomy. Approximately 60% of the cases were considered to be due to atherosclerosis, while the rest were attributed to atrial fibrillation or other reasons. We found that the majority of the thrombi contained oral streptococcal DNA. In the second study, we assessed the oral health of these patients and combined the results with their bacterial DNA findings and grade of carotid stenosis. We found that an association between poor oral health and acute ischemic stroke was linked to carotid artery atherosclerosis. In the third study, we confirmed the presence of viridans streptococci in the same thrombus aspirates that were used in the first study, employing bacterial immunohistochemistry. In addition, we performed immunohistochemistry on endarterectomy samples taken from symptomatic patients and on postmortem carotid artery samples taken from asymptomatic individuals. The samples taken from symptomatic patients contained considerably more viridans streptococci than those taken from asymptomatic individuals. Most of the streptococci were detected inside neutrophil granulocytes, but remnants of a bacterial biofilm as well as free bacterial infiltrates were also found in some samples.

The mechanism of how oral pathologies are related to the pathogenesis of ischemic stroke has been unclear. Immune responses that have evolved to combat bacterial infections are shared with those involved in the immune response to the inflammatory components of atherogenesis. Our results suggest that, along with the classical known risk factors, oral streptococcal inflammation may play an important role in the pathogenesis of ischemic stroke and that there may be a bacterial biofilm inside the arterial intima, affecting the development and rupture of the carotid plaque, which results in an ischemic stroke. Also, following transient bacteremia, streptococci entering the systemic circulation might promote thrombosis by activating platelets, eventually leading to the formation of a thromboembolism and causing an ischemic stroke, particularly in patients with atrial fibrillation. The possibilities of primary prevention of acute ischemic stroke by means of antibacterial vaccines and timed antimicrobial treatment, as well as regular dental care, should be considered.