Gut Microbiome

Correlation study between gut microbiota and intestinal permeability in cerebral small vessel disease.

TL;DR

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

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

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

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

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

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

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Citation

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