The gut microbiome is made up of tens of trillions of healthy and unhealthy microbes that play a major role in human health. As a growing collection of research helps to clarify the potential benefits of gut bacteria, a new study from Washington University School of Medicine demonstrates that the gut microbiome has a significant impact on brain health.
People with Alzheimer’s disease appear to have gut microbiomes that are different from those of healthy people, but it is not yet known whether these differences are a cause or a result of the disease. “Alzheimer’s disease (AD) is characterized by early deposition of amyloid-β (Aβ) plaques followed by pathological tau accumulation. Although Aβ is a necessary factor in AD pathogenesis, its accumulation in and of itself is insufficient for neurodegeneration and cognitive decline,” wrote the study authors.
“By contrast, pathological tau accumulation is closely linked with neurodegeneration and cognitive decline in AD and primary tauopathies. Alterations of the gut microbiota have been reported in AD, which suggests that the microbiota may contribute to AD progression.”
To investigate, the researchers altered the gut bacteria of mice that were predisposed to develop cognitive impairment. The study revealed that modified gut bacteria changed the behavior of immune cells throughout the body, including neural cells that promote brain damage that is associated withAlzheimer’s disease.
“We gave young mice antibiotics for just a week, and we saw a permanent change in their gut microbiomes, their immune responses, and how much neurodegeneration related to a protein called tau they experienced with age,” said study senior author Dr. David M. Holtzman. “What’s exciting is that manipulating the gut microbiome could be a way to have an effect on the brain without putting anything directly into the brain.”
Short-chain fatty acids are compounds produced by specific types of gut bacteria. The experts identified three short-chain fatty acids that were associated with neurodegeneration in the mice. Ultimately, these compounds activated immune cells in the brain that caused tissue damage.
Dr. Linda McGavern is the program director at the National Institute of Neurological Disorders and Stroke (NINDS), which provided some of the funding for the study. She noted that the study may offer important insights into how the microbiome influences tau-mediated neurodegeneration, and suggests therapies that alter gut microbes may affect the onset or progression of neurodegenerative disorders.
“What I want to know is, if you took mice genetically destined to develop neurodegenerative disease, and you manipulated the microbiome just before the animals start showing signs of damage, could you slow or prevent neurodegeneration?” said Dr. Holtzman.
“That would be the equivalent of starting treatment in a person in late middle age who is still cognitively normal but on the verge of developing impairments. If we could start a treatment in these types of genetically sensitized adult animal models before neurodegeneration first becomes apparent, and show that it worked, that could be the kind of thing we could test in people.”
The study is published in the journal Science.
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