Short-chain fatty acids improve poststroke recovery via immunological mechanisms

Rebecca Sadler, Julia V. Cramer, Steffanie Heindl, Sarantos Kostidis, Dene Betz, Kielen R. Zuurbier, Bernd H. Northoff, Marieke Heijink, Mark P. Goldberg, Erik J. Plautz, Stefan Roth, Rainer Malik, Martin Dichgans, Lesca M. Holdt, Corinne Benakis, Martin Giera, Ann M. Stowe, Arthur Liesz

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 (SCFAs), 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 SCFAs 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 remodeling. Further analyses confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFAs modulate poststroke recovery via effects on systemic and brain resident immune cells.

Original languageEnglish (US)
Pages (from-to)1162-1173
Number of pages12
JournalJournal of Neuroscience
Volume40
Issue number5
DOIs
StatePublished - Jan 29 2020

Keywords

  • Microbiome
  • Neuroinflammation
  • Plasticity
  • Stroke models

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Sadler, R., Cramer, J. V., Heindl, S., Kostidis, S., Betz, D., Zuurbier, K. R., Northoff, B. H., Heijink, M., Goldberg, M. P., Plautz, E. J., Roth, S., Malik, R., Dichgans, M., Holdt, L. M., Benakis, C., Giera, M., Stowe, A. M., & Liesz, A. (2020). Short-chain fatty acids improve poststroke recovery via immunological mechanisms. Journal of Neuroscience, 40(5), 1162-1173. https://doi.org/10.1523/JNEUROSCI.1359-19.2019