School of Medicine Publications and Presentations

The gut microbiome is associated with markers of cerebral small vessel disease

Document Type

Conference Proceeding

Publication Date




Cerebral small vessel disease (cSVD) is a major cause of cognitive impairment and dementia in the elderly. Dysregulation of the gut microbiome has been linked to cSVD, stroke, and dementia in human and animal studies. However, whether dysbiosis is associated with markers of cSVD is unclear. We aimed to assess the cross-sectional association between the gut microbiome and MRI markers of cSVD and executive function in the Framingham Heart Study (FHS).


We included FHS participants from the Third-generation cohort without a history of stroke or dementia. We estimated the gut microbiota composition using 16S rRNA gene sequencing. MRI markers of cSVD included white matter hyperintensities (WMH) and peak width of skeletonized mean diffusivity (PSMD). Executive function was assessed as the difference between the Trail Making Test (TMT) part B and A. We used multivariable regression analysis to evaluate the association between the gut microbiota and WMH, PSMD, and TMT, adjusting for age, age2, sex, BMI, and education. Additionally, we used differential abundance analysis to explore extremes of cSVD markers dichotomized by their distribution with the upper quintile representing the least healthy group. Finally, we used PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to gain insight into the functional profiles of the underlying microbial communities.


Our sample included 972 participants (age: 55 ± 10 years, 56% female). Using multivariable models, we found that greater abundance of genera Pseudobutyrivibrio and Ruminococcus were associated with lower (healthier) WMH and PSMD (p-values < 0.001), as well as better executive function (p-values < 0.01). Furthermore, the differential analysis indicated a lower abundance of the genus Prevotella in the group of participants with the highest (least healthy) PSMD and WHM (p-values < 0.05). Finally, functional analyses using PICRUSt implicated various KEGG pathways, including carbohydrate metabolism, glycosaminoglycan, and fatty acid biosynthesis previously associated with cognitive performance.


Our study suggests abundance of certain gut bacteria in genus Pseudobutyrivibrio, Ruminococcus, and Prevotella, that produce butyric acid and other metabolites used by the human brain, are associated with healthier brain vasculature and better cognitive function in middle-aged healthy adults.


© 2022 the Alzheimer's Association.

Publication Title

Alzheimer's & Dementia



Academic Level


Mentor/PI Department

Office of Human Genetics