Summary: The composition of the gut bacteria in individuals in the earliest stages of Alzheimer’s disease is significantly different from that in healthy people.
The discovery paves the way for the potential use of gut bacteria composition as a means of identifying individuals at higher risk of developing dementia. Additionally, it opens the door to designing preventative treatments that alter the gut microbiome to prevent cognitive decline.
However, the causal relationship between the gut and the brain remains to be fully determined.
Key facts:
- The study found that healthy individuals and those with early, presymptomatic Alzheimer’s disease had significantly different gut bacteria despite having similar diets.
- Differences in gut bacteria correlate with levels of amyloid beta and tau, proteins that accumulate in the brain before the cognitive symptoms of Alzheimer’s appear. However, no association with neurodegeneration was found.
- The researchers plan a five-year follow-up study to further investigate whether changes in the gut microbiome are a cause or a result of early Alzheimer’s disease.
source: WUSTL
People in the earliest stages of Alzheimer’s disease — after brain changes have begun but before cognitive symptoms become apparent — have a set of bacteria in their gut that differ from the gut bacteria of healthy people, according to a study by researchers at the School of Washington University Medicine in St. Louis.
The findings, published on June 14 in Scientific Translational Medicineopen the possibility of analyzing the gut bacterial community to identify people at higher risk of developing dementia and to design microbiome-altering preventive treatments to prevent cognitive decline.
“We don’t yet know whether the gut affects the brain or the brain affects the gut, but this connection is valuable to know either way,” said co-author Gautam Dantas, Ph.D., Conan Professor of Laboratory and Genomic Medicine.
“It is possible that changes in the gut microbiome are simply an indication of pathological changes in the brain. The other alternative is that the gut microbiome contributes to Alzheimer’s disease, in which case altering the gut microbiome with probiotics or fecal transfers may help alter the course of the disease.
The idea to study the relationship between the gut microbiome and Alzheimer’s disease emerged at a youth football game where Dantas and Bo M. Anses, MD, PhD, the Daniel J. Professor of Neurology. Brennan, they talked while their children played. Ances treats and studies people with Alzheimer’s disease; Dantas is an expert on the gut microbiome.
Scientists already knew that the gut microbiomes of people with symptomatic Alzheimer’s differed from the microbiomes of healthy people of the same age. But Anses told Dantas that no one has yet looked at the gut microbiomes of people in the critical pre-symptomatic phase.
“As long as people have cognitive symptoms, there are significant changes that are often irreversible,” said Anses, the other co-author.
“But if you can diagnose someone very early in the disease process, that would be the optimal time to effectively intervene with therapy.”
During the early stage of Alzheimer’s disease, which can last two decades or more, affected people accumulate clumps of the proteins amyloid beta and tau in their brains, but show no signs of neurodegeneration or cognitive decline.
Dantas, Ances, and first author Aura L. Ferreiro, Ph.D., then a graduate student in Dantas’s lab and now a postdoctoral researcher, assessed participants volunteering for training at the Charles F. and Joan Knight Alzheimer’s Research Center in Washington University. All participants were cognitively normal.
As part of this study, participants provided stool, blood, and cerebrospinal fluid samples; kept food diaries; and underwent a PET and MRI scan of the brain.
To distinguish participants who were already in the early stages of Alzheimer’s disease from those who were healthy, the researchers looked for signs of amyloid beta and tau accumulation through scans of the brain and cerebrospinal fluid. Of the 164 participants, about a third (49) had signs of early Alzheimer’s disease.
An analysis revealed that healthy people and people with preclinical Alzheimer’s disease have significantly different gut bacteria—in terms of the types of bacteria present and the biological processes in which those bacteria are involved—despite eating basically the same diet.
These differences correlated with levels of amyloid and tau, which rise before the onset of cognitive symptoms, but did not correlate with neurodegeneration, which becomes apparent around the time cognitive skills begin to decline. These differences could potentially be used to screen for early Alzheimer’s disease, the researchers said.
“The beauty of using the gut microbiome as a screening tool is its simplicity and ease,” Anses said.
“One day people may be able to provide a stool sample and find out if they are at increased risk of developing Alzheimer’s disease. It would be much easier and less invasive and more accessible to a large portion of the population, especially underrepresented groups, compared to brain scans or spinal taps.
Researchers have begun a five-year follow-up study aimed at finding out whether differences in the gut microbiome are a cause or a result of the brain changes seen in early Alzheimer’s disease.
“If there is a causal relationship, the most likely link is inflammatory,” said Dantas, who is also a professor of pathology and immunology, of biomedical engineering, of molecular microbiology and of pediatrics.
“Bacteria are these amazing chemical factories, and some of their metabolites affect inflammation in the gut or even end up in the bloodstream, where they can affect the immune system throughout the body.
“This is all speculative at this stage, but if it turns out that there is a cause-and-effect relationship, we can start to think about whether promoting the ‘good’ bacteria or removing the ‘bad’ bacteria could slow down or even stop the development of symptomatic Alzheimer’s disease.
For this Alzheimer’s research news
Author: Tamara Bhandari
source: WUSTL
Contact: Tamara Bhandari – WUSTL
Image: Image credit: Neuroscience News
Original research: Closed access.
“Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease” by Aura Ferreiro et al. Scientific Translational Medicine
Summary
Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease
Alzheimer’s disease (AD) pathology is thought to progress from normal cognition through preclinical disease and ultimately to symptomatic AD with cognitive impairment. Recent work suggests that the gut microbiome of symptomatic AD patients has an altered taxonomic composition compared to that of healthy, cognitively normal control individuals.
However, knowledge about changes in the gut microbiome before the onset of symptomatic AD is limited. In this cross-sectional study, which accounted for clinical covariates and dietary intake, we compared taxonomic composition and gut microbial function in a cohort of 164 cognitively normal individuals, 49 of whom showed biomarker evidence of early preclinical AD.
Gut microbial taxonomic profiles of individuals with preclinical AD are different from those of individuals without evidence of preclinical AD.
Alteration in gut microbiome composition correlates with β-amyloid (Aβ) and tau pathological biomarkers, but not neurodegeneration biomarkers, suggesting that the gut microbiome may change early in the disease process.
We identified specific gut bacterial taxa associated with preclinical AD. Inclusion of these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status when tested on a subset of the cohort (65 of 164 participants).
Gut microbiome correlates of preclinical AD neuropathology may improve our understanding of AD etiology and may help identify gut-derived markers of AD risk.