June 17, 2024

How gut bacteria may play a role in brain health

New research presented Wednesday at the Alzheimer’s Association International Conference in Amsterdam shows a growing body of evidence linking people’s microbiomes to their brain health.

​​​​One study found that chronic constipation was linked to worse cognitive abilities – the equivalent of three years of age – and two other studies found that certain gut bacteria were associated with dementia risk.

All three studies, which have not yet been published in peer-reviewed journals, point to a possible role for the build-up of “bad” bacteria in the gut in cognitive health.

“We know that regularly removing waste from the body is essential to overall good health. If that doesn’t happen, we can retain toxins that negatively impact our health in a variety of ways,” said Christopher Weber, director of global science initiatives at the Alzheimer’s Association, who was not involved in the research. “While more research is needed, it’s a great start.”

When ‘bad’ bacteria crowd out the ‘good’

Chaoran Ma, assistant professor of nutrition at the University of Massachusetts Amherst, led the study looking at constipation and cognitive decline, which analyzed data on bowel movements and cognition over six years from 110,000 people from three long-term studies.

People with chronic constipation – defined as one bowel movement every three days or more – were found to have “significantly” worse cognition, at three years of age, compared to those who could go once a day , the research found.

People with chronic constipation also had more bacteria that cause inflammation in their intestines and less bacteria that break down dietary fiber, said Ma, who was a research fellow at Brigham and Women’s Hospital and Harvard Medical School in Boston when the research was completed. The research showed correlation, not causation, which means the study does not prove that constipation causes such problems.

Researchers don’t know why constipation might affect the brain that way, but they speculate that the “good” type of defense is crowding out “bad” bacteria from building up, Weber said.

Ma said the findings are especially important for older adults, who are more likely to experience constipation due to lack of exercise, use of certain medications and diets deficient in fiber.

Two other studies presented at the conference, conducted by researchers at UT Health San Antonio in Texas, found that specific gut bacteria were associated with an increased risk of dementia in cognitively healthy adults. They found that other gut bacteria had protective effects.

Together, the findings add to a growing body of data about what scientists call the gut-brain axis—the two-way communication pathway that links the functions of the gastrointestinal tract and the brain through the nervous, immune, and hormonal systems and it is involved in a variety of processes, from metabolism to stress.

A better understanding of the axis could help scientists develop new ways to prevent and treat Alzheimer’s and other dementias even before symptoms develop.

“It’s important to recognize that all of our body systems are connected and working together,” Weber said. “If one of them is not working well and is not properly diagnosed and treated, it can have significant consequences for the health of other areas of the body.”

A biomarker of dementia in the womb?

Previous research found that people diagnosed with Alzheimer’s disease, as well as obesity, diabetes, irritable bowel syndrome and Parkinson’s. less diverse gut microbiome compared to those without the disease.

A study conducted in Japan and published last year in the journal Neurology & CNS Therapeutics found that Alzheimer’s patients with constipation experienced cognitive decline twice as fast as patients without constipation.

However, less is known about how – and whether – doctors will one day be able to use such gut changes to reliably identify dementia in people who still have healthy brains or treat it in those who have signs already.

“Everyone seems to have a unique microbiome, almost like a fingerprint,” said Dr. Monia Werlang, a gastroenterologist and clinical assistant professor at the University of South Carolina Greenville School of Medicine. “Scientists are still learning how to manipulate it to promote health and modify disease. Focusing on the microbiome is exciting, but there are a lot of unknowns, especially given the variability from person to person.”

Perhaps the biggest unknown is whether Alzheimer’s is caused by bacterial changes in the gut or whether bacterial changes in the gut, caused by constipation, for example, cause Alzheimer’s, said Rima Kaddurah-Daouk, co-principal investigator with the Protocol. Alzheimer’s Gut Microbiome Projecta collaborative research initiative mapping the brain-gut-brain axis and investigating how diet and other lifestyle interventions affect cognition.

Zooming in even more, are the bacteria themselves toxic to the brain, or are certain byproducts of the bacteria to blame?

“The bacteria that live with us are our partners, for better or for worse. Together we are finishing each other’s metabolism and producing many chemicals,” said Kaddurah-Daouk, who is a professor of psychiatry and behavioral sciences at Duke University School of Medicine in North Carolina. “The new research is a good first step, but we need to get to the molecular level and connect the dots.”

For example, a decrease in one bacterial byproduct, called butyrate, as detected in Ma’s study may partially explain why constipation is associated with poorer cognition.

Butyrate is produced in the gut when certain bacteria break down dietary fibre. It interacts with the immune system and helps reduce inflammation in the brain and spinal cord, Ma said. Butyrate also protects the blood-brain barrier, which helps prevent toxic molecules from entering the brain.

When there are fewer butyrate-producing bacteria, the brain becomes more vulnerable to invading “bad” molecules that can impair cognition. The natural aging process also favors an increase in inflammation-causing bacteria, which can lead to “leakage syndrome,” which allows toxic chemicals to travel into the brain, according to research published last year in the journal . Nutrients.

Although a “healthy” gut microbiome has yet to be defined, there is plenty of evidence to show that balance is key. In fact, an imbalance in the gut, known as dysbiosis, is linked to the development of anxiety, obesity, diabetes, depression, multiple sclerosis, chronic fatigue syndrome and other disorders, the same paper said.

More work is needed before experts can use the gut microbiome as a screening tool for Alzheimer’s and other dementias, which would be less invasive and more convenient than the brain scans or spinal taps currently used to diagnose the disease.

Dr. Shae Datta, a neuroscientist and co-director of NYU Langone’s Joint Intestinal Center, said that a biomarker like gut bacteria “could provide a window into dementia that could potentially help us start patients on medications and preventive methods with lifestyle modifications earlier, ” which is vital to treating Alzheimer’s.

Studies consistently show that exercise, adequate sleep and a proper diet consisting of foods rich in fiber (especially Mediterranean diet) will not only prevent constipation, but also promote brain health.

“It’s time to stop looking at Alzheimer’s as just a brain disease, but as a brain, liver and gut disease,” said Kaddurah-Daouk. “Changing your lifestyle—eating right, exercising, reducing stress—is more effective than any Alzheimer’s pill available today.”

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