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Researchers have discovered that gut bacteria may contribute to the process of neurodegeneration. However, it was unclear how bacteria could cause brain inflammation and degeneration until now. The study, published in Science, investigated mice with Alzheimer’s disease and found that gut bacteria that produce short-chain fatty acids could activate immune cells that trigger brain inflammation and worsen neurodegeneration. Germ-free mice and mice treated with antibiotics showed reduced signs of neurodegeneration compared to controls, suggesting that modulating the gut microbiota could help prevent or treat neurodegeneration.

Neurodegenerative conditions like Alzheimer’s disease are characterized by the accumulation of a protein called tau. Brain inflammation caused by another protein called apolipoprotein E (ApoE) is involved in the progression of tau-mediated neurodegeneration. Some studies have suggested that gut bacteria can regulate brain inflammation in mice that express a genetic variant of ApoE, which is considered the main genetic risk factor for Alzheimer’s disease. However, it was unclear if there was a causal link between gut bacteria and neurodegeneration.

To answer this question, researchers from the Washington University in St. Louis used a mouse model of Alzheimer’s disease to study how gut microbiota can influence tau-mediated neurodegeneration. They found that germ-free mice showed significantly less brain damage than mice with normal microbiota. Additionally, male mice treated with antibiotics at two weeks old showed less brain damage than controls, while female mice did not show reduced neurodegeneration.

The researchers also discovered that bacterial strains associated with short-chain fatty acid production could activate immune cells that trigger brain inflammation and worsen neurodegeneration. Levels of acetate, propionate, and butyrate were lower in mice treated with antibiotics and not detectable in germ-free mice. Providing germ-free mice with these fatty acids in their drinking water increased the activity of brain immune cells and signs of neurodegeneration.

The study offers insights into how gut bacteria influence tau-mediated neurodegeneration and suggests that modulating the gut microbiota could be a promising approach to preventing or treating neurodegenerative diseases like Alzheimer’s. However, the researchers noted that the response to microbiota manipulation could differ between sexes, as immune cells in male and female brains respond differently to stimuli. Further research is needed to determine how these findings could be applied to humans.

For more info: www.science.org