Patients with CSVD-associated cognitive impairment have gut microbiota imbalance and increased intestinal permeability associated with cognitive decline, and FMT from these patients can cause intestinal leakage and production of harmful metabolites in mice.
Key Findings
Results
Patients with CSVD-CI had higher incidence of hypertension, higher homocysteine levels, higher white matter hyperintensity scores, and worse cognitive function compared to healthy controls.
Study enrolled 21 patients with CSVD-CI and 20 healthy controls
CSVD-CI patients had higher incidence of hypertension than controls
CSVD-CI patients had higher homocysteine levels than controls
CSVD-CI patients had higher scores for white matter hyperintensities
CSVD-CI patients demonstrated worse performance on cognitive function assessments
Results
Urinary mannitol recovery rate was higher in CSVD-CI patients and correlated with lower cognitive function scores.
Intestinal permeability was assessed using the urine lactulose/mannitol ratio method
CSVD-CI patients showed a higher urinary mannitol recovery rate compared to healthy controls
The higher mannitol recovery rate was correlated with lower scores on cognitive function assessment
Mannitol recovery reflects small intestinal absorptive capacity and permeability changes
Results
Gut microbiota alterations in CSVD-CI patients included a reduction in Prevotella-9 and increases in Proteobacteria and Fusobacteria.
16S rRNA sequencing was used to analyze gut microbiota composition
Prevotella-9 was reduced in CSVD-CI patients compared to healthy controls
Proteobacteria were increased in CSVD-CI patients
Fusobacteria were increased in CSVD-CI patients
These changes represent dysbiosis of the gut microbiota in CSVD-CI
Results
Fecal microbiota transplantation (FMT) from CSVD-CI patients increased intestinal permeability in recipient C57 mice but did not alter their cognitive function.
Feces from CSVD-CI patients or healthy controls were gavaged into C57 mice
Gut barrier function, behavior, and metabolites were assessed in recipient mice
FMT from CSVD-CI patients increased intestinal permeability in mice
Cognitive function of recipient mice was not changed following FMT from CSVD-CI patients
Results
Fecal metabolomics analysis identified alterations in bile acids and vitamins in CSVD-CI patients that were associated with shifts in gut microbiota.
Fecal metabolomics analysis was performed on recipient mice following FMT
Alterations were identified in bile acid metabolites
Alterations were also identified in vitamin-related metabolites
These metabolic changes were associated with the observed shifts in gut microbiota composition
The altered metabolites were characterized as 'harmful metabolites' produced following FMT from CSVD-CI patients
Chen Y, Jie W, Xu Y, Chen X, Zhu S, Ma Y, et al.. (2026). Correlation study between gut microbiota and intestinal permeability in cerebral small vessel disease.. Journal of Alzheimer's disease : JAD. https://doi.org/10.1177/13872877261418554