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

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.