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Single-cell spatial transcriptomic profiling of 3xTg-AD mouse brains following fecal microbiota transplantation from stroke and healthy human donors

ABSTRACT: Stroke-induced gut dysbiosis has been linked to accelerated neurodegeneration, but whether stroke-altered microbiota alone can initiate Alzheimer's disease (AD) pathology remains unclear. We performed fecal microbiota transplantation (FMT) from human stroke and healthy donors into pre-symptomatic 3xTg-AD mice and profiled brain-wide gene expression using the NanoString CosMx Spatial Molecular Imager. Single-cell spatial transcriptomics revealed extensive cell-type-specific transcriptional remodeling in Stroke-FMT mice, including upregulation of genes involved in amyloid processing, neuroinflammation, and lipid metabolism, alongside downregulation of autophagy and calcium-signaling pathways. Region-specific analyses of cortex and hippocampus demonstrated convergent upregulation of AD-relevant drivers including Apoe, App, and Grin2b. These transcriptomic changes were accompanied by elevated phospho-Tau, GFAP, and IBA1 immunoreactivity and disrupted gut-brain redox and energy metabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE327581 | GEO | 2026/04/13

REPOSITORIES: GEO

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