Saccular intracranial aneurysms (IAs) are critical cerebrovascular diseases resulting from aberrant blood flow, inflammation, and arterial wall changes. These unruptured aneurysms are present in 1.8-3.2% of individuals in different populations and are generally asymptomatic. However, when they rupture, they lead to subarachnoid hemorrhage, a deadly condition with 35% mortality and long-term consequences in terms of disability and cognitive function.
Recent studies have focused on an important link between the microbiome and the pathogenesis of IAs, pointing out that the role of oral and gut microbiota extends much beyond the traditional health domains. Oral microecology, the second most diverse microbial community in the body after the gut interacts with systemic immunity and inflammation.
Population imbalance in the oral microbiota is regarded as dysbiosis, which is connected to the development of periodontal disease, oral cancer, diabetes, heart disease, Alzheimer’s, etc. A recent finding shows that oral microbes, especially Porphyromonas gingivalis, are also associated with cerebrovascular health because of inflammations and vascular remodeling.
Damage to the internal elastic layer of the cerebral artery, remodeling of collagen fibers, and disorganization of smooth muscle cells are seen in IAs. Such changes lead to weakness in the arterial wall and thus dilation, fibrosis, and eventually rupture. The immune cell-mediated inflammatory responses, usually activated by systemic metabolites and caused by microbiota dysbiosis, contribute significantly to aneurysm formation and development.
The endothelium is the innermost layer of blood vessels, which plays a critical role in maintaining vascular integrity and responding to hemodynamic stress. Endothelial dysfunction is usually driven by chronic inflammation and marks the earliest stages of aneurysm formation. Porphyromonas gingivalis, a periodontal pathogen, has been shown to exacerbate this dysfunction by infecting vascular smooth muscle cells (VSMCs) and activating signaling pathways that promote their migration, proliferation, and transformation. These processes compromise the structural integrity of the arterial wall, thereby predisposing it to rupture.
The outermost layer of blood vessels, adventitia, also plays a role in the formation of aneurysm pathogenesis. Fibroblasts within the adventitia regulate vascular remodeling and fibrosis, sensing vessel tension and allowing macrophage infiltration. Dysbiosis-induced inflammation amplifies these processes further, weakening the arterial wall.
The development of IA may be affected by oral microbiota dysbiosis through systemic pathways, including hematogenous spread of pathogens, alterations in the gut microbiome, and the oral gut-brain axis. Chronic inflammation induced by oral pathogens triggers extracellular matrix degradation, impaired vascular remodeling, and neuroinflammatory processes, which compromise cerebrovascular stability.
Studies have also shown that Porphyromonas gingivalis is a significant pathogen involved in this disease process. Other oral pathogens and their metabolites have been implicated in aneurysm pathogenesis, however, their causative roles are not fully established and thus require further study.
Balancing oral microbiota may offer a novel approach to preventing IAs. Systemic management of oral health by treatment of periodontal infections could lead to reduced systemic inflammation and less likelihood of aneurysm formation and rupture. Additionally, oral pathogens may also be monitored in patients with IAs, offering insight into the progression of the disease and its rupture risk.
Future studies should be aimed at investigating the broader spectrum of oral and gut pathogens implicated in aneurysm pathogenesis and assessing how genetic and environmental factors interact with microbiota dysbiosis. Longitudinal studies examining the impact of oral health interventions on IA outcomes are also crucial.
The connection between oral microbiota and intracranial aneurysms emphasizes the interconnectedness of systemic health. Dysbiosis of the oral microbiome contributes significantly to developing aneurysms, reflecting the need to approach healthcare management of patients in more integrated ways and may unlock newer strategic approaches in both prevention and control of this fatal condition.
Reference: Gong W, Yu H, You W, et al. The oral microbiota: new insight into intracranial aneurysms. Ann Med. 2025;57(1):2451191. doi:10.1080/07853890.2025.2451191
