Gut dysbiosis and complement-mediated neuroinflammation in vascular dementia
TL;DR
Interventions discussed in this review are presented not as clinical recommendations for the general population, but as potential translational targets requiring validation in clearly defined VaD or vascular cognitive impairment subgroups.
Abstract
Vascular dementia (VaD), the second most common form of dementia after Alzheimer’s disease, is increasingly understood as a heterogeneous disorder in which cerebrovascular injury interacts with endothelial dysfunction, blood–brain barrier disruption, systemic inflammation, and neuroimmune activation. This hypothesis-generating narrative review examines whether gut dysbiosis may contribute to VaD-relevant neuroinflammatory cascades through the microbiota–inflammation–leaky gut–leaky brain axis. In this framework, the vagus nerve is considered a bidirectional regulatory interface rather than a single linear pathway, while microbial metabolites such as lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO) are discussed as candidate links between intestinal barrier dysfunction, systemic inflammation, microglial priming, and complement-mediated synaptic vulnerability. The available evidence remains preliminary: most human studies are associative and many mechanistic findings derive from animal or in vitro models that cannot be directly translated to patients with VaD. Accordingly, the interventions discussed in this review are presented not as clinical recommendations for the general population, but as potential translational targets requiring validation in clearly defined VaD or vascular cognitive impairment subgroups.