Microbiome‐blood–brain barrier interactions in aging — mechanisms and therapeutic potential

Age‐related decline in neurovascular integrity is an increasingly recognized contributor to cognitive impairment and neurodegenerative vulnerability. A central feature is blood–brain barrier (BBB) dysfunction arising from endothelial senescence, altered barrier regulation, and chronic low‐grade inflammation. In parallel, aging remodels the gut microbiota, with reduced diversity, loss of short‐chain fatty acid‐producing commensals, and expansion of pro‐inflammatory taxa. Converging evidence indicates that age‐related shifts in the gut microbiota alter microbiome function and can modulate BBB physiology through microbial metabolites, immune‐endothelial signaling, and systemic metabolic pathways. These data position the gut–brain axis as an important, but not sole, modulator of neurovascular aging. Preclinical and emerging human data suggest that dysbiosis lowers the threshold for BBB dysfunction, and microbiome‐targeted interventions in experimental models can improve barrier‐relevant features. Notably, no human trial has yet demonstrated that microbiome modulation prevents or reverses BBB impairment using validated neuroimaging or fluid biomarkers. This review synthesizes mechanisms of microbiota‐BBB crosstalk in aging, distinguishes correlation from causation, and outlines translational opportunities and limitations of dietary, probiotic, and fecal microbiota‐based strategies for preserving neurovascular health in older adults.