Gut microbiota-mediated causal relations between sleep disorders and stroke: a Mendelian randomization study

Area of Science:

• Neuroscience
• Microbiology
• Epidemiology

Background:

• Sleep disorders are increasingly recognized as significant risk factors for stroke.
• The gut microbiota's role in overall health and disease pathogenesis is a growing area of research.
• However, the direct causal links between sleep disturbances, gut microbial composition, and stroke remain largely undetermined.

Purpose of the Study:

• To investigate the causal relationships between specific sleep disorders and stroke, including its subtypes.
• To explore the potential mediating role of the gut microbiota in the association between sleep disorders and stroke.
• To identify specific gut microbial taxa causally linked to stroke risk.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach to assess causality.
• Utilized the inverse variance weighted (IVW) method as the primary analytical strategy.
• Conducted sensitivity analyses for robustness and employed the coefficient product method to evaluate mediation effects.

Main Results:

• Insomnia showed a causal association with transient ischemic attacks (OR=1.592).
• Excessive daytime sleepiness was causally linked to ischemic stroke (IS) (OR=1.887).
• Sleep apnea demonstrated a causal association with overall stroke risk (OR=1.247), and Ruminococcus E sp900314705 was linked to increased stroke risk. Ezakiellaceae partially mediated the link between daytime sleepiness and IS (15.9% effect).

Conclusions:

• Established causal links between sleep disorders (insomnia, excessive daytime sleepiness, sleep apnea) and stroke.
• Identified specific gut microbiota taxa, including Ruminococcus E and Ezakiellaceae, associated with stroke risk.
• Highlighted the mediating role of Ezakiellaceae in the relationship between daytime sleepiness and ischemic stroke, underscoring potential therapeutic targets.