Invited Speaker Abstract Asia Pacific Stroke Conference 2024

Thinking beyond the brain: Long-term changes in the gut-brain-axis post-stroke (111358)

Rebecca J Hood 1 2 3 , Courtney B Cross 1 4 , Shannon M Stuckey 1 , Rosie A Costigan-Dwyer 1 , Samantha L Joubert 1 , Melissa Walker 1 , Tracy D Farr 5 , Mustafa Almuqbel 6 , Georgia Williams 7 , Hannah Rose Wardill 1 4 , Renee J Turner 1
  1. School of Biomedicine, University of Adelaide, Adelaide, SA, Australia
  2. School of Biomedical Sciences and Pharmacy, University of Newcastle, New Lambton Heights, NSW, Australia
  3. Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  4. South Australian Health and Medical Research Institute, Adelaide, SA, Australia
  5. School of Life Sciences, University of Nottingham, Nottingham, United Kingdom
  6. Department of Medical Radiography, University of Doha for Science and Technology, Doha, Qatar
  7. Preclinical Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Adelaide, SA, Australia

Background: 

Post-stroke secondary neurodegeneration (SND) involves progressive neuronal degeneration in regions remote to the stroke site and is linked to worsened outcomes in both clinical and preclinical studies.  Evidence suggests the microbiota-gut-brain axis (MGBA), a bi-directional communication network between the gut microbiota and the brain, may play a role in SND development.

Method: 

Thirty merino sheep (2-3y) underwent 2h middle cerebral artery occlusion followed by recovery out to 1-, 3-, or 6-months post-stroke (n=10/gp; 5M:5F).  T1W MRI, serum, cerebrospinal fluid (CSF) and faeces was collected pre-stroke and at endpoint. Ipsilateral thalamus volume was manually quantified using ITK Snap.  Microbiota composition of faecal samples was assessed using 16S rRNA gene sequencing. Serum and CSF endotoxin levels were determined using a limulus amebocyte colorimetric assay.

Results: 

PERMANOVA analysis revealed a compositional difference in the gut microbiota of faecal samples collected pre- vs. post-stroke (all timepoints combined, p=0.00015), which was underpinned by a reduction in the total number of operational taxonomic units present (p=0.0136). Furthermore, the change in beta diversity (PCo2) (pre-/post-stroke) correlated with decreased ipsilateral thalamus volume (r=-0.44, p=0.0011).  Increased endotoxin levels were also observed in both the serum (p=0.0493) and CSF (p=0.0002) post-stroke (all timepoints combined).

Conclusion: 

We show evidence of a relationship between gut microbiota changes and both brain atrophy and peripheral translocation of microbial endotoxins in post-stroke SND, thereby establishing a link between hallmarks of SND and gut microbiota dysregulation.  This highlights the MGBA as a potential target for therapeutics to prevent/halt SND.