Sleep Deprivation Exacerbates Ischemic Stroke Outcomes via Akkermansia Depletion and Metabolic Dysregulation

  • CNS Neurosci Ther. 2026 May;32(5):e70933. doi: 10.1002/cns.70933.
Xin Nie  1  2 ,  Sheng-Yang Zhou  2  3 ,  Le Yao  1 ,  Lu-Lu Tan  2  3 ,  Xiao-Yu Ma  2  3 ,  Yi-Meng Xia  2  3 ,  Chun Cui  2  3 ,  Wei-Jiang Zhao  2  3 ,  Chen-Meng Qiao  2  3 ,  Yan-Qin Shen  2  3 ,  Chao-Sheng Li  1  2
Affiliations
  • 1. Department of Neurology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
  • 2. Lab of Neurodegeneration and Injury, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
  • 3. MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
PMID: 42157727 DOI: 10.1002/cns.70933
Abstract

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.

Keywords
Akkermansia; gut microbiota; metabolite; middle cerebral artery occlusion; sleep deprivation.
Products