Gut microbes may improve stroke recovery

Summary: Microbiota-derived short-chain fatty acids (SCFA) modulate stroke recovery. The effect was mediated by circulating lymphocytes on microglia activation. The study reports SCFAs could be a potential therapeutic to improve post-stroke recovery.

Source: University of Kentucky

New research shows that the microorganisms in our gut could help protect brain cells from damage caused by inflammation after a stroke.

The study, published in the Journal of Neuroscience by researchers from the Ludwig Maximilian University of Munich, University of Kentucky’s College of Medicine and University of Texas Southwestern Medical Center reveals that supplementing the body’s short chain fatty acids could improve stroke recovery.

Short chain fatty acids, which are produced by the community of bacteria that live in the gut – known collectively as the microbiome – are a key component of gut health. Although it is known that the microbiome can also influence brain health and the central nervous system, its role in stroke recovery has not yet been explored.

“There is a growing amount of evidence that inflammation can be influenced by the microbiome, and now we are learning how it affects neuroinflammation after brain injury,” says Ann Stowe, UK associate professor in the Department of Neurology and co-author of the study.

Researchers added short chain fatty acids to the drinking water of mice, and those that drank the fatty acid water experienced a better stroke recovery. The fatty acid-supplemented mice had reduced motor impairment as well as increased spine growth on the dendrites of nerve cells, which are crucial for memory structure. They also expressed more genes related to microglia, the brain’s immune cells. This relationship indicates short chain fatty acids may serve as messengers in the gut-brain connection by influencing how the brain responds to injury.

The results could be promising news for stroke patients. Currently, there are only two FDA-approved treatments for acute stroke and no effective therapeutics to promote long-term repair in the brain after stroke damage.

A short chain fatty acid dietary supplement may be a safe and practical additional therapy for stroke rehabilitation, Stowe says.

New research by the University of Kentucky’s College of Medicine reveals that supplementing the body’s short chain fatty acids could improve stroke recovery. Image is adapted from the University of Kentucky news release.

“If we can confirm that a dietary supplement could be beneficial to inflammation and recovery after stroke, it could positively impact so many lives. We have nearly 800,000 people a year in the U.S. who are affected by stroke,” said Stowe.

The Centers for Disease Control and Prevention reports that stroke is also the number one cause of adult disability and the fifth leading cause of death in the U.S.

Stowe says the research collaboration with Dr. Arthur Liesz’ group in Munich is ongoing and next steps are to focus on additional behavioral tests as well as examining some of the specific immune cell populations that are affected by short chain fatty acids.

[divider]About this neuroscience research article[/divider]

Source:
University of Kentucky
Media Contacts:
Elizabeth Chapin – University of Kentucky
Image Source:
The image is adapted from the University of Kentucky news release.

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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