Gut Microbiome in Sporadic Cerebral Small Vessel Disease: MRI-Defined Phenotypes, Mechanistic Evidence, and...

Cerebral small vessel disease (CSVD) is a major vascular component of brain aging, yet potentially modifiable systemic contributors remain incompletely understood. Growing evidence links the gut microbiome to magnetic resonance imaging (MRI)-defined CSVD, but interpretation is complicated by heterogeneity in microbiome profiling, clinical populations, analytical methods, and neuroimaging phenotypes. This review critically integrates the available human evidence with complementary multi-omics, ex vivo, and experimental findings.

PubMed, Embase, Scopus, and Web of Science were searched through 4 August 2026; 12 eligible reports representing eight cohort families were included and evaluated using a structured study-level methodological appraisal.

Across the available literature, ecological and host-related biological processes show greater qualitative convergence than individual taxa, although this pattern has not been formally quantified across independent cohorts. Among reported alpha diversity measures, Chao/Chao1 showed the same numerical disease-versus-control direction across four cohort families, with statistical significance in two, suggesting a recurrent but still preliminary richness-related signal; Shannon and Simpson indices were less consistent. No single genus or species has been consistently replicated across the available, largely cross-sectional cohorts. Complementary studies implicate intestinal barrier, immune-metabolic, neurovascular, and perivascular clearance pathways but do not establish a unified causal pathway in human sporadic CSVD.

These observations support a hypothesis-generating ecosystem-level framework. Because diet is an important modifiable determinant of the gut microbial ecosystem, these findings may have relevance for nutrition-based strategies targeting vascular brain aging. However, no CSVD-specific dietary or microbiome-directed intervention has yet been shown to modify disease progression or related MRI outcomes.