Harnessing the microbiome to improve stroke recovery

Summary: Short-chain fatty acid supplementation improves stroke recovery in mouse models.

Source: SfN

Supplementing the body’s short chain fatty acids can improve stroke recovery, according to research in mice recently published in Journal of Neuroscience. Short chain fatty acid supplementation may be a non-invasive addition to stroke rehabilitation therapies.

The gut microbiome influences brain health, including how the brain recovers from stroke. Short chain fatty acids, a fermentation product from the bacteria in our guts, are a key component of gut health but their role in stroke recovery has not been explored.

Sadler et al. added short chain fatty acids to the drinking water of mice for four weeks before inducing a stroke. The mice that drank the fatty acid water experienced a better stroke recovery compared to the control mice, including reduced motor impairment and increased spine growth on dendrites – a crucial memory structure. Additionally, the fatty acid-supplemented mice expressed more genes related to microglia, the brain’s immune cells.

This shows a graphic abstract

Post-stroke neuronal plasticity is altered by short-chain fatty acid treatment. Image is credited to Sadler et al., JNeurosci 2019.

Microglia activity could be responsible for increasing dendritic spines and improving stroke outcome.

This relationship indicates short chain fatty acids may serve as messengers in the gut-brain connection by influencing how the brain responds to injury.

About this neuroscience research article

Source:
SfN
Media Contacts:
Calli McMurray – SfN
Image Source:
The image is credited to Sadler et al., JNeurosci 2019.

Original Research: Closed access
“Short-Chain Fatty Acids Improve Post-Stroke 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 and Arthur Liesz.
Journal of Neuroscience doi:10.1523/JNEUROSCI.1359-19.2019.

Abstract

Short-Chain Fatty Acids Improve Post-Stroke Recovery via Immunological Mechanisms

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.

SIGNIFICANCE STATEMENT

Previous studies have shown a bi-directional communication along the gut-brain axis after stroke. Stroke alters the gut microbiota composition, and in turn, microbiota dysbiosis has a substantial impact on stroke outcome by modulating the immune response. However, until now the mediators derived from the gut microbiome affecting the gut-immune-brain axis and the molecular mechanisms involved in this process were unknown. Here, we demonstrate that SCFA—fermentation products of the gut microbiome—are potent and pro-regenerative modulators of post-stroke neuronal plasticity at various structural levels. We identified that this effect was mediated via circulating lymphocytes on microglial activation. These results identify SCFA as a missing link along the gut-brain axis and as a potential therapeutic to improve recovery after stroke.

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