Gut microbiota and cerebrovascular diseases: a Mendelian randomization study

Area of Science:

• Genetics
• Microbiology
• Epidemiology

Background:

• The link between gut microbiota and cerebrovascular disease is not well understood.
• Recent studies suggest an association, but causal relationships require further investigation.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and cerebrovascular disease.
• To identify specific bacterial taxa influencing cerebrovascular disease risk.
• To examine the mediating roles of systolic blood pressure (SBP), type 2 diabetes (T2D), and body mass index (BMI).

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics.
• Reverse MR analysis to assess bidirectional causality.
• Two-step MR to evaluate mediation by SBP, T2D, and BMI.
• Sensitivity analyses to ensure result robustness.

Main Results:

• A high abundance of Porphyromonadaceae family bacteria was associated with reduced intracranial aneurysm risk.
• Nominal causal relationships were found between seventeen gut microbiota and intracranial aneurysms.
• Thirteen to eight gut bacteria showed nominal causal links with stroke and its subtypes.
• Genetically predicted stroke (AS, AIS) reduced the abundance of Clostridiaceae1 and Clostridiales.
• Genus Streptococcus effects were mediated by T2D; Eubacterium brachy group effects by SBP.

Conclusions:

• Gut microbiota composition exerts a causal influence, either beneficial or detrimental, on cerebrovascular disease.
• Systolic blood pressure and type 2 diabetes are identified as potential mediators in the gut microbiota-cerebrovascular disease axis.