The current study explores the relationship between genetically predicted gut metabolites and functional outcomes following ischemic stroke, utilizing the Mendelian Randomization (MR) framework. Genetic information regarding gut microbiota-derived metabolites was sourced from 2076 participants of European descent participating in the Framingham Heart Study. Data on functional outcomes 90 days post-ischemic stroke were acquired from the Genetics of Ischemic Stroke Functional Outcomes Network (n = 6,021). Genetic proxies for gut microbiota were identified from a large-scale GWAS study by the MiBioGen consortium, encompassing 18,340 samples across 24 distinct cohorts. The inverse variance weighting method served as the primary analytical approach. Host gene-influenced gut microbiota was linked to both favorable and unfavorable functional outcomes post-ischemic stroke, involving nine and two specific microbiomes, respectively. Moreover, genetically predicted metabolites of gut microbiota showed associations with functional outcomes post-ischemic stroke, exhibiting one positive and five negative correlations. Sensitivity analyses employing alternative methods and models, not adjusted for baseline stroke severity, consistently supported these findings. This research provides genetic substantiation of the influence of specific gut microbiota and metabolites on the recovery process following ischemic stroke, suggesting a potential causal relationship. This insight offers valuable perspectives on the trajectory of post-stroke recovery and prognostic development.
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