[Roles of growth factor-mediated brain-gut axis crosstalk in neurorepair following ischemic stroke]

In recent years, the brain-gut axis, a critical bidirectional signaling pathway between the central nervous system and the gut microbiota, has attracted increasing attention for its role in the pathological progression of ischemic stroke (IS). Cell growth factors, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), are not only classical neuroprotective molecules but may also act as key signaling mediators of brain-gut axis communication because of their multifaceted roles in intestinal barrier regulation, peripheral immune remodeling, and central-peripheral crosstalk. Gut microbiota metabolites, such as short-chain fatty acids, tryptophan metabolites, and bile acid derivatives, can regulate BDNF, NGF, IGF-1, and VEGF through the PI3K/Akt and MAPK/ERK pathways, thereby affecting synaptic plasticity, neuronal survival, angiogenesis, and neural repair. The downstream signals of these factors converge on shared core pathways, producing functional additivity and synergistic effects. Based on these mechanisms, intervention strategies such as probiotic supplementation (e.g., Bifidobacterium bifidum), prebiotics or dietary fiber (e.g., inulin and arabinoxylan), natural product modulation (e.g., diosmetin, rhubarb extract, and cornuside), and fecal microbiota transplantation can reshape the gut microbiota, increase metabolites such as short-chain fatty acids, regulate tryptophan metabolism, and inhibit inflammatory pathways such as TLR4/NF-κB. These interventions indirectly upregulate endogenous growth factors, including BDNF, IGF-1, and FGF, and activate signaling pathways such as PI3K/Akt, MAPK/ERK, and BDNF/TrkB/CREB, thereby reducing cerebral infarct volume, improving neurological and cognitive function, alleviating post-stroke depression, and promoting hippocampal neurogenesis, thus demonstrating considerable neuroprotective potential. This review focuses on the interrelationships among cell growth factors, the brain-gut axis, and IS, explores how growth factors act as messengers of the brain-gut axis and play a bridging role in the pathological progression of IS, and discusses novel therapeutic strategies targeting this axis.