Metab Brain Dis. 2026 May 25;41(1):114. doi: 10.1007/s11011-026-01881-1.
ABSTRACT
Post-stroke sleep disorder (PSSD) is a common but underrecognized complication of ischemic stroke, affecting neurological recovery and quality of life. Emerging evidence suggests a role for the gut-brain axis (GBA) in regulating sleep and post-stroke inflammation, yet the microbiome and metabolomic signatures of PSSD remain poorly defined. This study aimed to characterize the gut microbiota and metabolic profiles of PSSD patients, identify potential biomarkers, and explore potential microbial-metabolite-clinical associations. A total of 42 ischemic stroke patients (17 with PSSD, 25 without) and 23 healthy controls were enrolled. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Fecal samples were analyzed by 16 S rDNA sequencing and untargeted metabolomics, and KEGG pathway enrichment were used to integrate multi-omic data and clinical parameters. Age and serum lymphocyte levels were independent risk factors for PSSD. PSSD patients exhibited enriched pro-inflammatory genera such as Veillonella and Citrobacter. Metabolomic profiling demonstrated elevated histamine and hesperetin in PSSD, along with decreased 6-Dimethylaminopurine and LysoPE(0:0/18:3). Integrated microbiota-metabolite-host analyses revealed correlations between differential taxa, metabolites, and clinical indices, including PSQI scores, HDL-C, and inflammatory markers. Our findings indicate that PSSD is associated with a distinct gut microbial and metabolic signature, highlighting potential mechanistic links through neuroinflammation, neurotransmitter imbalance, and disrupted energy metabolism. These results provide a foundation for developing gut-targeted biomarkers and therapeutic strategies for post-stroke sleep disorders.
PMID:42178430 | DOI:10.1007/s11011-026-01881-1