Gut Microbiome and Cerebral Vasospasm
The connection between the gut microbiome and cerebral vasospasm is an emerging area of research in neuroscience and microbiology.
Potential Links Between Gut Microbiome and Cerebral Vasospasm
Inflammation:
The gut microbiome significantly influences systemic inflammation. Dysbiosis, an imbalance in the gut microbiome, can lead to increased intestinal permeability (“leaky gut”), allowing endotoxins such as lipopolysaccharides (LPS) to enter the bloodstream. Elevated levels of LPS can trigger systemic inflammatory responses, which might exacerbate cerebral inflammation and contribute to vasospasm.
Immune Modulation:
The gut microbiome modulates the immune system. Certain bacterial metabolites, such as short-chain fatty acids (SCFAs), play a role in maintaining the blood-brain barrier and regulating neuroinflammation. Dysbiosis might disrupt this regulation, potentially leading to increased susceptibility to cerebral vasospasm. Neurotransmitter Production:
Gut bacteria produce various neurotransmitters and neuromodulators (e.g., serotonin, GABA). These can influence brain function and vascular tone. Alterations in the production of these compounds due to microbiome changes could affect cerebral blood vessels and contribute to vasospasm. HPA Axis and Stress Response:
The gut microbiome interacts with the hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress responses. Dysregulation of the HPA axis due to gut microbiome alterations might influence vascular tone and susceptibility to vasospasm following brain injuries. Research and Clinical Implications Research into the gut-brain axis has revealed the significant role of the gut microbiome in neurological health and disease. Understanding the connection between the gut microbiome and cerebral vasospasm could lead to new therapeutic strategies, such as:
Probiotics and Prebiotics: Modulating the gut microbiome with probiotics (beneficial bacteria) or prebiotics (compounds that promote the growth of beneficial bacteria) might help prevent or treat cerebral vasospasm. Dietary Interventions: Diet plays a crucial role in shaping the gut microbiome. Dietary modifications could potentially mitigate the risk of vasospasm by promoting a healthy microbiome. Anti-inflammatory Treatments: Targeting inflammation through microbiome-based approaches could offer new avenues for preventing or managing cerebral vasospasm. Conclusion While the research on the gut microbiome and cerebral vasospasm is still in its early stages, the potential connections are compelling. Further studies are needed to elucidate the mechanisms involved and to explore potential therapeutic interventions that target the gut microbiome to prevent or treat cerebral vasospasm.
An imbalance within the intestinal microbiota, referred to as dysbiosis, was suggested to play a role in the formation, progression, and rupture of IA. As no systematic review on this topic exists, considering the significance of this matter and a lack of effective prophylaxis against IA or cerebral vasospasm, we aim to sum up the current knowledge regarding their associations with intestinal microbiome, identify the gaps, and determine future prospects. Scientific databases were systematically and independently searched by two authors from inception to 1st May 2023 for original articles regarding the role of intestinal microbiota in intracranial aneurysmal growth, aSAH occurrence, as well as in cerebral vasospasm following aSAH. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist was followed in an abstraction process. The STROBE tool was applied to assess the risk of bias. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 302 records, four studies were included that fully met eligibility criteria. Studies reported (1) that the relative abundance of Hungatella hathewayi is a protective factor against aneurysm growth and rupture, resulting from the reduced inflammation and extracellular matrix remodeling in the cerebral arterial wall and from reduced metalloproteinase-mediated degradation of smooth muscle cells in cerebral vessels. (2) Relative abundance of Campylobacter ureolyticus is associated with aSAH. (3) No article has evaluated microbiota in relation to cerebral vasospasm following aSAH although there is an ongoing study. We concluded that intestinal microbiota might be a potential target for diagnostic and therapeutic tools to improve the management of cerebral aneurysms. However, more studies of prospective design are needed 1).
Tomasz Klepinowski et al in a first pilot study aimed to test study feasibility and identify differences in gut microbiota between subjects with and without CVS following aSAH. A prospective nested case-control pilot study with 1:1 matching was conducted recruiting subjects with aSAH: cases with CVS; and controls without CVS based on the clinical picture and structured bedside transcranial Doppler (TCD). Fecal samples for microbiota analyses by means of 16S rRNA gene amplicon sequencing were collected within the first 96 h after ictus. Operational taxonomic unit tables were constructed, diversity metrics calculated, phylogenetic trees built, and differential abundance analysis (DAA) performed. At baseline, the groups did not differ significantly in basic demographic and aneurysm-related characteristics (p > 0.05). Alpha-diversity (richness and Shannon Index) was significantly reduced in cases of middle cerebral artery (MCA) vasospasm (p < 0.05). In DAA, relative abundance of genus Acidaminococcus was associated with MCA vasospasm (p = 0.00013). Two butyrate-producing genera, Intestinimonas and Butyricimonas, as well as [Clostridium] innocuum group had the strongest negative correlation with the mean blood flow velocity in anterior cerebral arteries (p < 0.01; rho = - 0.63; - 0.57, and - 0.57, respectively). In total, 16 gut microbial genera were identified to correlate with TCD parameters, and two intestinal genera correlated with outcome upon discharge. In this pilot study, they prove study feasibility and present the first preliminary evidence of gut microbiome signature associating with CVS as a significant cause of stroke in subjects with aSAH 2).