Gut bacteria responsible for brain cell death and reduced cognitive functions with age have been found

A group of American researchers has discovered a molecule produced by bacteria of the intestinal microbiome (including humans) and capable of penetrating into the brain, causing the death of neurons and other cells. The effect is especially noticeable with age, when the number of these bacteria increases markedly, which can lead to a decrease in cognitive functions, such as learning and memory.

Micrograph of microglia cells colored green and neuronal bodies colored red / © Chen Zh. et al., Nature Communications, 2014

The intestinal microbiome is a collection of all microorganisms inhabiting the gastrointestinal tract and living mainly in mutually beneficial relationships with the host organism. For example, intestinal bacteria help us digest and assimilate various substances (the same fiber) and play an important role in the synthesis of vitamins B and K. In the process of vital activity, the microbiome releases many molecules, some of which can cause harm to the host body, among other things.

This was confirmed by the authors of a new study published in the journal Cell Host & Microbe. They studied the family of bacteria Ruminococcaceae inhabiting the intestines of mice (but also found in humans), and the small molecule they secrete — isoamylamine (IA). Scientists found that the older the mouse got, the more these bacteria were in its intestinal microbiome, and, as a result, the content of IA increased.

The IAA molecule interested researchers even more when it turned out that it was able to overcome the blood—brain barrier – a protective system that usually prevents any unwanted molecules and microorganisms from entering the brain from the bloodstream. Next, scientists determined the role of the IAA molecule in the brain.

A brief description of the principle and result of the action of the isoamylamine molecule (IAA) on brain microglia / © Yun Teng et al, Cell Host & Microbe, 2022

It turned out that it affects microglia — auxiliary cells of the central nervous system involved in the formation and maintenance of contacts between nerve cells, as well as the destruction of various kinds of “garbage”, such as damaged neurons or other brain cells. IA activates a special gene S100A8, which promotes excessive activation of microglia (as in the inflammatory process), which can lead to the death of neurons and other brain cells due to an autoimmune process (microglia attacks even whole and healthy cells).

To find out the consequences of getting IaaS into the brain, the authors of the work orally (through the mouth) injected a drug containing IaaS into young healthy mice and observed the reaction. As a result of several behavioral and cognitive tests, it turned out that exposure to IaaS led to a loss of cognitive function: rodents became worse at learning to navigate in a maze and recognize objects. The reverse effect was observed when scientists blocked the action of IA on microglia in elderly mice: this provoked an improvement in memory and spatial learning.

Thus, the researchers were able to establish the presence and mechanism of action of a molecule produced by an intestinal bacterium on brain cells and cognitive functions using the example of mice. Nevertheless, scientists admit that more research will be needed to find out whether these findings apply to humans and whether blocking the action of IaaS can prevent cognitive decline as people age or in the case of certain neurodegenerative diseases.

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