Gut microbiome intervention in gut-brain axis and effects on vascular dementia with prospects on non-pharmacological intervention

Vascular dementia (VD) is the second leading cause of cognitive impairment after Alzheimer's disease. Current treatments focus primarily on managing vascular risk factors with no effective interventions for repairing existing brain damage. Recent research underscores a critical link between gut microbiota and brain function through immunological, hormonal and metabolic pathways. Alterations in the gut microbiome influence vascular cognitive impairment via mechanisms such as dysbiosis, induced intestinal permeability, systemic inflammation, oxidative stress and blood-brain barrier disruption. Microbial metabolites including butyrate promote neuroprotection and maintain vascular integrity, whereas trimethylamine N-oxide is associated with vascular injury and cognitive decline. Restoration of microbial balance through probiotics, plant-based bioactive compounds and traditional medicines has shown potential in preclinical models for regulating inflammation, improving cognitive outcomes though clinical validation is limited. Non-pharmacological approaches like electro-acupuncture further modulate the microbiome and serotonin regulation. This review explores how changes in gut microbiome influence vascular cognitive impairment and discusses therapeutic strategies for restoring microbial balance. Integrating contemporary and traditional strategies, gut microbiome modulation emerges as a potential therapeutic target for the prevention and management of VD although its clinical applicability remains to be fully established.