What if modifying the intestinal flora prevented neuronal degeneration?

by time news

There is growing evidence 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 performedna a key role in the health of our brainoaccording to researchers at the Washington University School of Medicine in St. Louis (USA).

The work, done 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, which can damage tissue. brain and exacerbate neurodegeneration in conditions such as Alzheimer’s disease. The results, published in the journal “Science”, open up the possibility of modifying the intestinal microbiome to prevent or treat neurodegeneration.

“We gave young mice antibiotics for just one week and saw a permanent change in their gut microbiome, their immune response, and the degree of neurodegeneration related to a protein called tau that they experienced with age,” he explains. David M. Holtzman, lead author of the study. “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.”

There is increasing evidence that the gut microbiome of people with Alzheimer may differ from that of healthy people. But it is not clear whether these differences are the cause or the result of the disease – or both – and what effect altering the microbiome might have on the course of the disease.

To determine whether the gut microbiome may be playing a causative role, the researchers altered the gut microbiomes of mice predisposed to developing Alzheimer’s-like brain damage and cognitive decline. The mice were genetically engineered to express a mutant form of the human brain protein tau, which accumulates and causes neuron damage and atrophy in their brains by 9 months of age. They were also carriers of a variant of the human APOE gene, one of the main genetic risk factors for Alzheimer’s. People with one copy of the APOE4 variant are between three and four times more likely of developing the disease than people with the more common APOE3 variant.

When these genetically modified 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 harboring normal microbiomes.

When these mice were raised under normal, non-sterile conditions, they developed normal microbiomes. However, treatment with antibiotics at two weeks of life, it permanently changed the bacterial composition of its microbiomes. In the case of male mice, it also reduced the amount of brain damage evident at 40 weeks of age. The protective effects of microbiome changes were more pronounced in male mice carrying the APOE3 variant than in the high-risk APOE4 variant, possibly because the deleterious effects of APOE4 abolished some 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 issues, that immune cells of male and female brains respond to way different from the stimuliYes,” Holtzman says. “So it’s not terribly surprising that when we manipulated the microbiome we observed a sex difference in response, although what exactly this means for men and women with Alzheimer’s disease and related disorders is hard to say.”

Other experiments related tthree specific fatty acids short-chain -compounds produced by certain types of intestinal bacteria as products of their metabolism- with neurodegeneration. These three fatty acids were scarce in mice with gut microbiomes altered by antibiotic treatment, and undetectable in mice without gut microbiomes.

The findings suggest a new approach to prevent and treat neurodegenerative diseases by modifying the gut microbiome with antibiotics, probiotics, specialized diets

“This study may offer important information on how the microbiome in tau-mediated neurodegenerationand suggests that therapies that alter gut microbes may affect the onset or progression of neurodegenerative disorders,” says Linda McGavern.

Findings suggest a new approach to prevent and treat neurodegenerative diseases by modifying the microbiome intestinal with antibiotics, probiotics, specialized diets or other means.

“What I want to know is if you take mice genetically destined to develop neurodegenerative diseases and manipulate the microbiome just before the animals start to show signs of damage, could that slow or prevent neurodegeneration?” Holtzman wonders. “That would be equivalent to starting treatment in a late-middle-aged person who is still cognitively normal but is on the verge of developing deficiencies. If we could start a treatment in these kinds of genetically sensitized adult animal models before neurodegeneration first sets in, and show that it works, that might be the kind of thing we could test in people.”

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