The Association between Cerebral Small Vessel Disease and the Gut Microbiome: A Cross-Sectional Analysis

Naoki Saji, Kenta Murotani, Takayoshi Hisada, Tsuyoshi Tsuduki, Taiki Sugimoto, Ai Kimura, Shumpei Niida, Kenji Toba, Takashi Sakurai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Background: Recent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear. Materials and Methods: We performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome. Results: We analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity. Conclusions: The gut microbiome is associated with cerebral SVD.

Original languageEnglish
Article number105568
JournalJournal of Stroke and Cerebrovascular Diseases
Issue number3
Publication statusPublished - 2021 Mar


  • Cognitive decline
  • Dementia
  • Gut
  • Microbiome
  • Small vessel disease
  • White matter hyperintensity

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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