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Gut bacteria affect brain health

Summary: Gut bacteria affect the behavior of immune cells throughout the body and in the brain, including those implicated in neurodegenerative disorders such as Alzheimer’s disease. The findings open up the possibility of altering the microbiome to prevent or treat neurodegeneration.

Source: WUSTL

A growing pile of evidence indicates that the tens of trillions of microbes that normally live in our intestines – the so-called gut microbiome – have far-reaching effects on how our bodies function. Members of this microbial community produce vitamins, help us digest food, prevent the overgrowth of harmful bacteria, and regulate the immune system, among other benefits.

Now, a new study suggests that the gut microbiome also plays a key role in the health of our brains, according to researchers at Washington University School of Medicine in St. Louis.

The study, in mice, found that gut bacteria — in part by producing compounds like short-chain fatty acids — affect the behavior of immune cells throughout the body, including those in the brain that can damage brain tissue and exacerbate neurodegeneration. in conditions such as Alzheimer’s disease. illness.

The findings, published Jan. 13 in the journal Scienceopen the possibility of remodeling the intestinal microbiome as a way to prevent or treat neurodegeneration.

“We gave young mice antibiotics for just one week and saw a permanent change in their gut microbiomes, their immune responses, and how much neurodegeneration related to a protein called tau they experienced as they age,” said senior author David M. Holtzman, MD, Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology.

“What’s exciting is that manipulating the gut microbiome could be a way to affect the brain without putting anything directly into the brain.”

Evidence is accumulating that the gut microbiomes in people with Alzheimer’s disease may differ from those in healthy people. But it’s unclear whether these differences are the cause or result of the disease — or both — and what effect changing the microbiome might have on the course of the disease.

To determine whether the gut microbiome might be playing a causal role, the researchers altered the gut microbiomes of mice predisposed to developing Alzheimer’s-like brain damage and cognitive impairment.

The mice were genetically engineered to express a mutated form of the human brain tau protein, which builds up and causes damage to neurons and atrophy in their brains by 9 months of age.

They also carried a variant of the human SUPPORT gene, an important genetic risk factor for Alzheimer’s disease. People with a copy of APOE4 variant are three to four times more likely to develop the disease than people with the more common one. APOE3variant.

Along with Holtzman, the research team included gut microbiome expert and co-author Jeffrey I. Gordon, MD, Dr. Robert J. Glaser Distinguished University Professor and Director of the Edison Family Center for Genome Sciences & Systems Biology; first author Dong-Oh Seo, PhD, an instructor in neurology; and co-author Sangram S. Sisodia, PhD, professor of neurobiology at the University of Chicago.

When these genetically engineered mice were raised in sterile conditions from birth, they did not acquire gut microbiomes and their brains showed much less damage at 40 weeks of age than the brains of mice that harbored normal mouse microbiomes.

When these mice were reared under normal, non-sterile conditions, they developed normal microbiomes. A 2-week-old course of antibiotics, however, permanently changed the makeup of the bacteria in their microbiomes. For male mice, it also reduced the amount of brain damage evident at 40 weeks of age.

The protective effects of microbiome changes were most pronounced in male virus-carrying mice. APOE3 variant than in those at high risk APOE4variant, possibly because the deleterious effects of APOE4canceled part of the protection, the researchers said. Antibiotic treatment had no significant effect on neurodegeneration in female mice.

“We already know from studies of brain tumors, normal brain development and related topics that immune cells in male and female brains respond very differently to stimuli,” said Holtzman.

“So it’s not all that surprising that when we manipulated the microbiome, we saw a sex difference in response, although it’s hard to say exactly what this means for men and women living with Alzheimer’s disease and related disorders.”

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This shows a diagram of the study

Other experiments have linked three specific short-chain fatty acids – compounds produced by certain types of gut bacteria as products of their metabolism – to neurodegeneration. All three of these fatty acids were scarce in mice with gut microbiomes altered by antibiotic treatment and undetectable in mice without gut microbiomes.

These short-chain fatty acids appeared to trigger neurodegeneration by activating immune cells in the bloodstream, which in turn somehow activated immune cells in the brain to damage brain tissue. When middle-aged mice lacking microbiomes were fed the three short-chain fatty acids, their brain immune cells became more reactive and their brains showed more signs of tau-related damage.

It shows the outline of a head
Evidence is accumulating that the gut microbiomes in people with Alzheimer’s disease may differ from those in healthy people. The image is in the public domain

“This study may offer important insights into how the microbiome influences tau-mediated neurodegeneration and suggests that therapies that alter gut microbes may affect the onset or progression of neurodegenerative disorders,” said Linda McGavern, PhD, program director at the National Institute of Neurological Disorders. and Stroke (NINDS), who provided some of the funding for the study.

The findings suggest a new approach to preventing and treating neurodegenerative diseases by modifying the gut microbiome with antibiotics, probiotics, specialized diets or other means.

“What I want to know is, if you took mice that were genetically destined to develop neurodegenerative diseases and you handled the microbiome just before the animals started to show signs of damage, could you delay or prevent neurodegeneration?” Holtzman asked.

“This 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 disabilities. If we could start a treatment in these types of genetically sensitized adult animal models before the neurodegeneration became apparent and show that it worked, this could be the kind of thing we could test in people.”

About this microbiome and neuroscience research news

Author: Judy Martin Finch
Source: WUSTL
Contact: Judy Martin Finch – WUSTL
Image: The image is in the public domain

Original search: Discoveries will appear in Science