Short-chain fatty acids improve post-stroke recovery via immunological mechanisms.
J Neurosci. 2019 Dec 30. pii: 1359-19. doi: 10.1523/JNEUROSCI.1359-19.2019. [Epub ahead of print]
|Authors/Editors:||Sadler R, Cramer JV, Heindl S, Kostidis S, Betz D, Zuurbier KR, Northoff BH, Heijink M, Goldberg MP, Plautz EJ, Roth S, Malik R, Dichgans M, Holdt LM, Benakis C, Giera M, Stowe AM, Liesz A.|
Recovery after stroke is a multicellular process encompassing neurons, resident immune cells and brain-invading cells. Stroke alters the gut microbiome which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut-brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFA), key bioactive microbial metabolites, are the missing link along the gut-brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed that SCFA induced altered contralesional cortex connectivity. This was associated with SCFA-dependent changes in spine and synapse densities. RNA-sequencing of the forebrain cortex indicated a potential involvement of microglial cells in contributing to the structural and functional re-modelling. Further analyses confirmed a substantial impact of SCFA on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFA modulate post-stroke recovery via effects on systemic and brain resident immune cells.