Could Alzheimer's Have Origins in the Gut?

THURSDAY, June 15, 2023 (HealthDay News) -- People with early markers of Alzheimer's disease in the brain also have alterations in their gut bacteria, a new study finds — hinting at a potential way to identify people at risk of dementia, and possibly even treat them.

Any such tests or treatments would be years away, experts said.

But the findings — published June 14 in the journal Science Translational Medicine — add to a growing body of evidence linking the gut microbiome to Alzheimer's.

The term refers to the trillions of bacteria and other microbes that dwell in the gut and play a critical role in digestion and many other bodily functions — from immune defenses, to producing vitamins, anti-inflammatory compounds and even chemicals that influence the brain.

An explosion of research in recent years has been looking into links between the gut microbiome and various health conditions, including heart disease, depression and degenerative brain diseases like Parkinson's and Alzheimer's.

The question is whether certain gut microbiome profiles — an abundance of particular "bad" bacteria or short supply of some "good" ones — might contribute to those diseases.

Past studies have found that the gut microbiome of Alzheimer's patients looks different from that of other older adults.

Now the new study shows that such differences are apparent in the "preclinical" phase of Alzheimer's. That's the period where two proteins — amyloid and tau — are abnormally clumping in the brain, but the person is not yet suffering dementia symptoms.

"We're seeing gut microbiome changes pretty early in the disease," said Dr. Beau Ances, one of the principal researchers on the study.

That does not prove the microbiome alterations actually help cause Alzheimer's, said Ances, a professor of neurology at Washington University School of Medicine in St. Louis. It's possible the disease process in the brain drives changes in the gut.

But if the gut microbiome is a "causative" factor, Ances said, that would open up possibilities for treating early Alzheimer's: Could probiotics or fecal transplants from healthy donors be used to shift the microbiome away from a pro-Alzheimer's profile, and change the course of the disease?

Those questions will take years of research to work out, said Robert Vassar, director of the Mesulam Center for Cognitive Neurology and Alzheimer's Disease at Northwestern University Feinberg School of Medicine, in Chicago.

But the new findings "add significantly to the story," said Vassar, who was not involved in the study.

"It's been known for a little while that there are changes in the gut microbiome of patients with Alzheimer's," he said. "We didn't know that this precedes symptoms."

Researchers made the discovery by analyzing stool samples from 164 adults, aged 68 to 94, who were enrolled in health studies at their university. All had undergone brain imaging and lumbar puncture to get spinal fluid samples, as well as tests of their cognition (memory and thinking skills).

While everyone in the group had normal cognition, about one-third did show an abnormal build up of amyloid and tau in the brain.

And that group, the researchers found, typically had a gut microbiome that was different from other participants' — in terms of the species of bacteria they harbored and some of the functions those bacteria were performing.

Why would microbes in the gut have anything to do with a brain disease?

It's not fully clear yet, but both Ances and Vassar pointed to chronic inflammation — which is believed to play a key role in many diseases, including Alzheimer's. The abnormal protein deposits in the Alzheimer's-affected brain appear to create a chronic inflammatory state, Vassar said.

Certain gut bacteria secrete acids and chemicals that can thin and seep through the intestinal lining, creating a "leaky kind of gut," Ances said. It's possible that inflammatory chemicals from the gut get into the brain and help feed inflammation there.

Research in lab mice hints that the gut microbiome could be a good target for early-Alzheimer's therapies: Manipulating the gut bacteria of mice with Alzheimer-like brain disease can reduce amyloid deposits, for instance.

Any human therapies are a long way off, though.

"We still have a lot of work to do in this field," Vassar said. That includes figuring out exactly which gut bacteria are the bad guys, and which might help shield the brain.

Even without proof that gut bacteria are causing trouble, they could still be helpful in the quest for earlier Alzheimer's diagnosis, Ances said. Eventually, it might be possible to use a simple stool test to identify people at increased risk of the disease.

For now, Vassar said there are ways for people to support their brain health.

"In general," he said, "what's good for the heart is good for the brain."

That includes a diet low in processed foods, red meat and sugar, and closer to the Mediterranean-style of eating: Lots of fish, vegetables, fiber-rich grains and "good" fats from sources like olive oil and nuts.

Regular exercise and sufficient sleep are also critical, Vassar said. Exercise has well-known heart and vascular benefits, he noted, but physical activity — and a good night's sleep — may also help the brain more efficiently clear itself of amyloid.

More information

The Alzheimer's Association has advice on supporting brain health.

SOURCES: Beau Ances, MD, PhD, professor, neurology, Washington University School of Medicine in St. Louis; Robert Vassar, PhD, director, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago; Science Translational Medicine, June 14, 2023, online