The Role Oral Microbiome in the Development and Progression of Vascular Diseases

Background According to the statement by the World Health Organization, cardiovascular diseases are currently the primary cause of death. Around 202 million people are suffering from lower extremity arterial disease worldwide. The occurrence of moderate to severe carotid artery stenosis is less frequent, with a prevalence of only 4.2% according to recent reports. However, it can be a probable cause of TIA or stroke in 12-25% of acute ischemic strokes. Fortunately, the prevalence of abdominal aortic aneurysms and incidence rates have decreased over the last 20 years, which has been attributed partially to the decline in smoking.

Aortic aneurysms are the most common dilations in the human body, which occur primarily in the abdominal aorta section. The disease affects approximately 1-5% of the adult population. Its main risk factors include age over 65, smoking, and male gender. The exact pathomechanism of the disease is still unknown but the importance of degenerative (atherosclerosis, fibromuscular dysplasia, cystic media degeneration), congenital (Marfan syndrome, Ehlers-Danlos syndrome, coarctation aortae), mechanical (traumatic, iatrogenic, post stenotic) and inflammatory (bacterial, autoimmune) factors arise. The pathological role of atherosclerosis mainly emerges in the background of the degenerative processes that develop in the walls of blood vessels. In addition, based on the latest scientific research results, knowledge of the systemic autoimmune processes involved in the etiology of aortic aneurysms and the consequent local inflammatory mechanisms is of particular importance.

According to our latest scientific knowledge at a molecular level, histopathological classification, tissue transformation, mapping of the degradation of structural proteins that weaken the aortic wall, spatial aspects, and immunological factors all contribute to the development of aneurysms. Although the importance of immunological processes seems to be crucial, the precise contribution of the immunological factors to the aneurysm formation is largely unknown. A wide variety of abnormal immunological responses associated with inflammation and autoimmunity in the vessel wall are known, such as loss of immune tolerance, activation of pro-inflammatory cytokines, age-related vascular wall remodeling, and immunosenescence. Clinically, large vessel vasculitis and vasculitis associated with other systemic autoimmune diseases may play a role in the development of aneurysms through the shift in these immunological processes. Inflammatory processes may persist for years in addition to the remission of these diseases, promoting the development of aneurysms years after diagnosis of vasculitis. On the other hand, the importance of persistent subclinical local inflammatory processes in the development of aneurysms, which does not show a clinical picture of large vessel vasculitis, also arises. Gut microbiota dysbiosis and microbiome pattern is also an important cause of aneurysm formation. In summary, knowledge of local immunological processes and microbiome patterns involved in the etiology of aortic aneurysms may promote improved diagnosis and treatment.

The coincidence of peripheral vascular diseases and poor oral health has been a well-observed phenomenon in recent years. Periodontitis is an oral disease that is highly prevalent worldwide. It is an inflammatory disease affecting about 50% of the global population, its severe form is present in more than 750 million people, therefore it is the 6th most prevalent disease in mankind. In Europe, alone the prevalence of mild to moderate periodontitis is 40-60%, and of severe periodontitis, it is 10-20%. The inflammatory process starts with dental plaque collecting on the tooth surface in patients with inadequate oral hygiene containing hundreds of microbial species. This bacterial biofilm causes a reversible gingival inflammation known as gingivitis, but if untreated and neglected, it may progress to periodontitis in patients where periopathogenic species dominate. This in turn induces an inflammatory host response and burdens the immune system. Periodontitis is the leading cause of adult tooth loss due to the breakdown of teeth-supporting tissues. Furthermore, it may induce inflammatory processes in other parts of the body, such as the nervous system, and the cardiovascular system. Whether the relationship between oral and vascular lesions is causal or not is unclear, but periodontal pockets act as a portal for bacterial entrance into the circulation. Understanding the microbiome of symptomatic and asymptomatic patients may help in the early detection and possible prevention of symptomatic manifestations of carotid artery stenosis.

More and more evidence has been published about the potential relationship between periodontal and cardiovascular diseases. According to the published results, a correlation was revealed between the severity of periodontal disease and pathogen load detected from vascular samples of atherosclerotic plaques and aneurismatic walls. Although, a microbiomial pattern, compatible with oral samples was found in only 21% of samples taken from carotid plaques.