Author ORCID Identifier

https://orcid.org/0000-0002-6141-9150

Date Available

8-9-2022

Year of Publication

2022

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department/School/Program

Neuroscience

First Advisor

Ai-Ling Lin, PhD

Second Advisor

Joe Springer, PhD

Abstract

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and may play a role in stroke rehabilitation. A severely imbalanced microbial community has been shown to occur following stroke, causing a systemic flood of neuro- and immunomodulatory substances due to increased gut permeability and decreased gut motility. Here we measure post-stroke increased gut dysbiosis and how it correlates with gut permeability and subsequent cognitive impairment.

We recruited 12 participants with acute stroke, 12 healthy control participants, and 18 participants who had risk factors for stroke, but had not had a stroke. We measured the gut microbiome with whole shotgun sequencing on stool samples. We measured cognitive and emotional health with MRI imaging and the NIH toolbox. We normalized all variables and used linear regression methods to identify gut microbial levels associations with cognitive and emotional assessments.

Beta diversity analysis revealed that the bacteria populations of the stroke group were statistically dissimilar from the risk factors and healthy control groups. Relative abundance analysis revealed notable decreases in butyrate-producing microbial taxa. The stroke group had higher levels of the leaky gut marker alpha-1-antitrypsin than the control groups, and roseburia species were negatively correlated with alpha-1-antitrypsin. Several Actinobacteria species were associated with cerebral blood flow and white matter integrity in areas of the brain responsible for language, learning, and memory. Stroke participants scored lower on the picture vocabulary and list sorting tests than those in the control groups. Stroke participants who had higher levels of roseburia performed better on the picture vocabulary task.

We found that microbial communities are disrupted in a stroke population. Many of the disrupted bacteria have previously been reported to have correlates to health and disease. This preparatory study will lay the foundation for the development of therapeutics targeting the gut following stroke.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2022.301

Funding Information

This research was supported by grants from NIH/NIA, NIH/ODS, and American Federation for Aging Research to A-LL (R01AG054459 and RF1AG062480) and TCH (T32AG057461).

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