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Published on: November 14, 2025
Sleep Deprivation Exacerbates Ischemic Stroke Outcomes via Akkermansia Depletion and Metabolic Dysregulation
Xin Nie1,2, Sheng-Yang Zhou2,3, Le Yao1
1Department of Neurology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Aims:
Sleep disturbances are a potential risk factor for stroke. Our clinical cohort shows that insomnia is associated with a higher 90-day stroke recurrence rate, prompting an investigation into the underlying mechanisms, particularly the role of the gut microbiota.
Methods:
We utilized a rat MCAO model of sleep deprivation (SD) combined with antibiotic (ABX)-induced gut dysbiosis. Neurological deficits were assessed through behavioral tests, and cerebral infarct volume was measured using TTC staining. Structural changes in brain and intestinal tissues were observed by H&E staining, while the expression of blood-brain barrier (BBB)-related proteins was detected by immunofluorescence and Western blot. Gut microbial composition was analyzed by 16S rRNA sequencing, and metabolomic analysis was performed using an untargeted LC-MS approach.
Results:
In rats with an intact microbiota, SD had a limited effect on MCAO-induced ischemic injury. Strikingly, in ABX-induced dysbiosis, SD-exposed rats subjected to MCAO displayed more severe motor deficits, larger infarct volumes, heightened inflammation, and decreased expression of key intestinal and BBB proteins. Microbiota analysis identified Akkermansia as a potential key mediator, whose abundance was significantly decreased in the ABX + SD + MCAO group and negatively correlated with infarct size. Subsequent metabolomics profiling revealed a distinct dysregulation of Akkermansia-associated metabolites (including PG(14:0/15:0), 3-Methylbutylamine, N-Acetylcytidine, and N-Methylisoleucine).
Conclusion:
In conclusion, our study proposes a mechanism whereby SD worsens stroke outcomes by depleting Akkermansia and disrupting metabolic homeostasis.
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