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30 - 05 - 2017

A link between intestinal microbiota and stroke highlighted in mice

A new study in mice reinforces the theory that intestinal bacteria influence the cerebral vascular system. This work could lead to preventive stroke treatments for people at risk.

 A link between intestinal microbiota and stroke highlighted in mice


A scientific team from the University of Pennsylvania (USA) discovered an unexpected link between blood vessels in the brain and intestinal bacteria, or microbiota.

The team has been working more specifically on cerebral cavernous malformations (CCMs), clusters of dilated blood vessels that can cause blood leakage in brain tissue and lead to seizures or strokes. The work was published in the journal Nature on the 10th of May.



A accidental discovery that lead to new experiments


The researchers worked on a well-established model of mice that develop MCCs after the injection of a drug. The team found that when the animals were transferred to new premises, the frequency of MCC formation dropped.

Alan Tang, a student-researcher, found that transferred mice that still had MCCs also had abscesses that contained Gram-negative bacteria. Injected into healthy mice, these bacteria caused MCCs in half the animals, as well as spleen abscesses. Therefore the bacteria penetrated the bloodstream and had access to the blood vessels in the brain.



A signaling pathway involved, and soon a drug?
Gram-negative bacteria produce substances called lipopolysaccharides (LPS), potent activators of the innate immunity. Injecting LPS into mice results in the appearance of MCCs similar to those produced by the Gram-negative bacterial infection. However, when the LPS receptor is eliminated, the mice no longer exhibit MCCs. This concurs with the fact that in humans, the overactivation of this receptor by a mutation leads to an increased risk of MCCs.

The LPS signaling pathway is therefore a prime target for possible preventive treatments of stroke and epileptic seizures in people with MCCs, especially considering that a drug blocking the LPS receptor is currently being studied to treat sepsis.

Another approach, validated by these researchers in mice, would be to act on the microbiota, in order to reduce the number of MCCs and the risk of stroke.

Many studies still need to be conducted, but these studies provide a better understanding of the links between the intestinal microbiota and the health of the brain.


Hélène Bour


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