Longxue tongluo capsule enhances ischemic stroke recovery via microbiota-metabolite-gene interactions

The gut-brain axis represents an emerging therapeutic target. This study seeks to investigate the regulatory effects of LXTL on the brain-gut axis and to elucidate its mechanism of action during the ischemic stroke recovery period. This study investigated the effects of LXTL on a middle cerebral artery occlusion and reperfusion model. The assessment of recovery effects was conducted through the evaluation of brain injury scores, Y-maze performance, open field tests. Furthermore, comprehensive analyses were conducted on the gut microbiota, damaged brain tissue, cecal contents, and brain samples using metagenomic sequencing, transcriptomic sequencing, and non-targeted metabolomics. And the selected targets were verified. Integrated analyses were conducted by constructing correlation networks and performing joint pathway enrichment to elucidate the connections between microbial alterations, metabolite changes, and gene expression modifications. LXTL improved cognitive and exploratory behaviors, reduced brain damage and neuron loss, and enhanced gut health by increasing beneficial bacteria like Eubacterium and Kurthia. It boosted SCFAs, neuroactive metabolites, and altered nucleotide metabolism. LXTL is linked to genes involved in neurorepair and immune homeostasis, correlates with microglial polarization, and is associated with genes such as Ngfr, Card9, Chat, Nkg7, and Gch1 within the pertinent pathways. The integrated network linked LXTL-enhanced microbiota, gut and brain metabolites, and repair genes, facilitating recovery through a neurorepair-immune-metabolic triad. LXTL aids ischemic stroke recovery by altering gut microbiota and gut-brain metabolite profiles, while regulating brain gene networks related to neuroplasticity, inflammation, and metabolism. This demonstrates LXTL's multi-target effects through the gut-brain axis, underscoring the potential of herbal medicine in stroke rehabilitation.