People in the earliest stage of Alzheimer's disease, prior to the onset of cognitive symptoms, have a different assortment of bacteria in their intestines than healthy individuals, a study has found.
The research opens up the possibility of using gut bacterial analysis to identify those at higher risk of developing dementia and to design treatments that alter the microbiome to prevent cognitive decline.
“We don’t yet know whether the gut is influencing the brain or the brain is influencing the gut, but this association is valuable to know in either case,” said co-corresponding author Gautam Dantas, Conan Professor of Laboratory and Genomic Medicine at Washington University in St Louis, Missouri.
Dr Dantas pointed out that there are two main possibilities.
One is that the changes in the gut microbiome are a reflection of pathological changes in the brain.
The alternative is that the gut microbiome contributes to Alzheimer's disease, and that changing it might alter the disease's course.
The idea of examining the gut microbiome's connection to Alzheimer's originated from a casual conversation between Dr Dantas and Beau M Ances, the Daniel J Brennan Professor of Neurology, during a children's football game.
Dr Ances, who studies and treats Alzheimer's patients, spoke with Dr Dantas, an expert on the gut microbiome, about the lack of research into the gut microbiomes of people in the pre-symptomatic phase of Alzheimer's.
“By the time people have cognitive symptoms, there are significant changes that are often irreversible,” Dr Ances explained.
However, if someone is diagnosed very early in the disease process, therapeutic intervention can be more effective.
During the study, the team evaluated participants who volunteered at the Charles F and Joanne Knight Alzheimer Disease Research Centre at Washington University.
To identify those in the early stage of Alzheimer's, they looked for signs of amyloid beta and tau accumulation using brain scans and cerebrospinal fluid.
They found that about a third of the 164 participants showed signs of early Alzheimer's.
Their analysis revealed significant differences in gut bacteria between healthy people and those with preclinical Alzheimer's, regardless of a largely similar diet.
The differences, which correlated with amyloid and tau levels, did not correlate with neurodegeneration, suggesting their potential use as early Alzheimer's screening tools.
According to Dr Ances, using the gut microbiome as a screening tool is advantageous due to its simplicity and accessibility.
Dr Ances envisions a future where people can provide a stool sample to assess their risk of developing Alzheimer's, an approach that would be less invasive and more accessible than brain scans or spinal taps.
The team has initiated a five-year follow-up study to determine whether these differences in gut microbiome are a cause or a result of the brain changes seen in early Alzheimer's.
Dr Dantas noted that if a causative link is found, it could likely be inflammatory.
“Bacteria are these amazing chemical factories, and some of their metabolites affect inflammation in the gut or even get into the bloodstream, where they can influence the immune system all over the body,” he said.
“All of this is speculative at this point, but if it turns out that there is a causal link, we can start thinking about whether promoting ‘good’ bacteria or getting rid of ‘bad’ bacteria could slow down or even stop the development of symptomatic Alzheimer’s disease.”
The research was carried out by researchers at the Washington University School of Medicine and was published in Science Translational Medicine.