- There is increasing evidence that people with Alzheimer’s may have different gut microbiomes than people without the condition.
- Experts do not yet know whether these differences in the microbiome are a cause or a result of Alzheimer’s disease.
- New research has shown that altering the gut microbiome changes the behavior of immune cells in the brain in mice.
- The researchers suggest that manipulating the gut microbiome may be a new approach to preventing and treating Alzheimer’s and other neurodegenerative diseases.
As the prevalence of Alzheimer’s disease (AD) continues to increase, the search for ways to treat and prevent it is ever more pressing. Newly licensed treatments, such as aducanumab and lecanemab, that clear
Many researchers are now focusing on other areas, one of which is the effect of the
Now, a new study from Washington University School of Medicine in St. Louis has found that gut bacteria affect immune responses in the brains of mice.
By changing the gut bacteria in mice that had been genetically modified to develop AD neuropathologies, the researchers altered the amount of
The study was published in Science.
It is widely acknowledged that the microbiome affects overall health, but it is only within the past 15 years that researchers have started to recognize the importance of the so-called gut-brain axis.
“Many diseases of the body and mind are now linked to gut microbiota, including Alzheimer’s disease.”
— Dr. Jennifer Bramen, Ph.D., senior research scientist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California
A person’s microbiome
“There is growing recognition of a gut-brain axis and evidence that the microbiome of individuals varies with disease status. The biggest issue is understanding whether gut changes are due to disease or contribute to disease (or both).”
— Dr. M. Kerry O’Banion, professor of neuroscience at the Del Monte Institute for Neuroscience at the University of Rochester
Neurodegeneration from certain bacteria
The mice in this latest study were genetically modified to develop Alzheimer’s-like brain damage and cognitive impairment. All of them carried a variant of the APOE gene, which is a genetic risk factor for AD, and expressed a mutant form of the tau protein that is found in the human brain. The
The mice were divided into 2 groups. One group was raised in sterile conditions from birth, so did not develop any microbiome, while the others were given antibiotics early in life to permanently change the composition of their microbiome.
All the mice were fed a typical lab diet, although food for the sterile group was autoclaved to destroy any bacteria. They were moved regularly to sterile cages to avoid contamination from old droppings in their cages.
At 40 weeks, researchers euthanized the mice and examined their brains.
The brains of mice that had been kept in sterile conditions from birth showed much less neurodegeneration than the brains of mice with typical mouse microbiomes.
For the mice given antibiotic treatment, there was a difference between the sexes. Male mice showed less brain damage than female mice given the same treatment. This difference was most pronounced in male mice carrying the
Senior author Dr. David M. Holtzman, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology, commented:
“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. So it’s not terribly surprising that when we manipulated the microbiome we saw a sex difference in response, although it is hard to say what exactly this means for men and women living with Alzheimer’s disease and related disorders.”
The researchers found that three short-chain fatty acids produced by certain types of gut bacteria were linked to neurodegeneration.
These fatty acids were absent in mice with no microbiome and at very low levels in those that had been given antibiotics. The researchers suggest that these fatty acids were activating immune cells that damaged brain tissue.
To test this, they fed these three fatty acids to middle-aged mice with no microbiome. Their brain immune cells then became more active, and their brains subsequently showed more signs of tau-linked damage.
The findings offer insights into how the microbiome might influence tau-mediated neurodegeneration in humans. The researchers suggest that modifying the gut microbiome with antibiotics, probiotics, specialized diets, or other means might be a new approach to preventing and treating neurodegenerative diseases, such as AD, in people.
“Many researchers believe that work aimed at unpacking the complex influence of the gut microbiome on Alzheimer’s disease will lead to new therapeutics to prevent and mitigate neurodegeneration.”
— Dr. Jennifer Bramen
There is increasing evidence that a healthy
Dr. O’Banion said that the current study “helps establish causality and bring hope that modifying the human microbiome might impact health by preventing or altering diseases.”
However, the findings must be treated with caution as
“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?”
— Dr. David Holtzman