An older adult woman cooking near a windowShare on Pinterest
Changes in the gut microbiome could one day be used to detect Alzheimer’s. Tatyana Aksenova/Getty Images
  • People at high risk of Alzheimer’s disease exhibit changes in their gut bacteria long before symptoms appear.
  • It has been known for some time that people with disease symptoms have different microbiomes, but this study “moves the goalposts” earlier in the disease’s progression, according to an expert.
  • Although more research is needed to understand the relationship between these microbiotas and Alzheimer’s, physicians may be able to forgo expensive diagnostic procedures in favor of relatively simple analyses of gut bacteria.
  • If subsequent research finds that the bacteria play a causal role in Alzheimer’s, microbiota cocktails — in the form of a pill — may be on the menu for people with the disease.

Researchers have known for some time that gut bacteria, or microbiota, of people with Alzheimer’s disease is not like that of other people. A new study provides evidence that this difference significantly pre-dates the disease.

The study finds that people who are likely to get Alzheimer’s have its characteristic gut microbiota profile long before they experience symptoms of the disease.

The study leaves open, for now, an obvious and important underlying question. Is it this microbiome imbalance that causes Alzheimer’s, or is it an indicator of the disease’s presence?

While the researchers from Washington University School of Medicine in St. Louis, Missouri are conducting follow-up research to answer this question, their study raises intriguing possibilities:

  • Can future Alzheimer’s be diagnosed early on simply by analyzing a person’s gut bacteria?
  • Can existing Alzheimer’s be treated by making a therapeutic change to the microbiome?

The study is published in Science Translational Medicine.

According to Dr. Tharick Pascoal, associate professor of psychiatry and neurology at the University of Pittsburgh, who was not involved in this study, the findings “sugges[t] that abnormalities in the microbiota are present very early in the disease and may play a role in its development, rather than being a mere consequence as some early theories postulated.”

“What this study does is it moves the goalposts even earlier in the disease process,” said Dr. Pascoal.

Although the gut is located far from the brain, there are a few hypotheses regarding their possible interaction in Alzheimer’s.

“The gut microglia may be associated with activation of glial cells in the brain.” said Dr. Pascoal. “The resultant neuroinflammatory process has already been linked with cognitive problems for many previous studies.”

Dr. Robert J. Vassar, professor of Alzheimer’s Research at Northwestern University, suggested another mechanism. “We think that it’s likely to be short-chain fatty acids.”

“We hypothesize that it’s the short-chain fatty acids that the bacteria produce that get into the bloodstream, and certain ones of them may get into the brain and cause Alzheimer’s or at least modify the Alzheimer’s pathology,” he explained.

His Center for Cognitive Neurology and Alzheimer’s Disease has been studying the role of the microbiome in Alzheimer’s with mice, and “what we find is that if we alter the gut microbiome, for example, using a cocktail of antibiotics, we will change the Alzheimer’s pathology in the brain of the mice.”

“So there is a connection between the gut, at least in the mouse, and the Alzheimer’s pathology in the brain,” said Dr. Vassar.

Among the defining traits of Alzheimer’s disease are amyloid-protein plaques that build up on the brain’s neurons, and tangles of tau proteins that the plaques encourage.

Alzheimer’s has an extended early stage that can last 10 to 20 years before any symptoms appear. During this time, plaques begin to form and can be detected with brain scans.

While the plaques sometimes occur in people who do not go on to develop Alzheimer’s, they are one of the indicators physicians use to detect the disease. They were observed in the study’s population of individuals who had early microbiome changes.

Since the study is cross-sectional, it cannot explore a possible causal relationship between microbiota changes and Alzheimer’s, or the other way around. To separate cause from effect, a five-year longitudinal follow-up study has already been designed.

The current study’s corresponding author, Dr. Beau M. Ances said: “We are longitudinally following individuals. We also hope to look at individuals as they progress to symptomatic Alzheimer’s disease. We hope to also study individuals with symptomatic Alzheimer’s disease.”

Dr. Vassar suggested how researchers might resolve the question.

“If I were them, I would plan a study where they would screen cognitively [healthy] people for the Alzheimer’s biomarkers in the brain, and I would choose a group of people that had clean brains with no Alzheimer’s biomarkers,” he said.

Recognizing that it is likely that some of the latter group will one day develop Alzheimer’s, he proposed following the entire cohort over time, administering cognitive tests, performing brain scans, and sampling their gut bacteria.

Then researchers could reexamine the microbiome and see whether there were any changes or if there were differences from the start, said Dr. Vassar.

“You may find out that there are some people that, from the very beginning, have a different gut microbiome,” he said.

“These results could be very important, as we show simple measures from the stool in combination with additional measures have a good ability to identify individuals with preclinical Alzheimer’s disease,” said Dr. Ances.

If the study’s results are further confirmed, such simple tests could replace expensive and unpleasant brain scans and spinal taps as diagnostic methods for Alzheimer’s.

In addition, if it turns out that microbiota causes or influences the progression of Alzheimer’s, it may be possible, envisioned Dr. Vassar, to formulate simple oral medications. “Cocktails” containing AD-beneficial bacteria or beneficial short-chain fatty acids could help prevent, slow, or treat the disease.