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Changes in Gut Bacteria May Be an Early Alzheimer’s Sign

3D render of the inside of the gut, with gut microbes.
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A study from Washington University School of Medicine in St. Louis shows that gut bacteria in people with pre-symptomatic Alzheimer’s disease (AD) may differ compared to healthy people. The research, published in Science Translational Medicine, may lead to future diagnostics or treatments for AD that target the gut microbiome.

Insights into the gut microbiome

AD is a neurodegenerative disease and form of dementia that causes memory and cognitive skills to decline. It is characterized by abnormal proteins such as amyloid beta plaques and tau tangles that build up in the brain and result in the loss of neurons.

AD can cause brain changes up to two decades before the onset of symptoms. During this early preclinical stage, amyloid beta and tau can accumulate in the brain without any signs of neurodegeneration or cognitive decline.

Previous research has revealed that the gut microbiomes of people with symptomatic AD differ to those of healthy people at the same age.

What is the gut microbiome?

The gut microbiome is a community of microbes – including bacteria, fungi, viruses and protozoa – that reside in our gut. It carries out a variety of functions that help to regulate our health, such as stimulating the immune system, aiding digestion and synthesizing key vitamins.

However, no research to date has focused on the gut microbiomes of people in this pre-symptomatic stage.

AD and the gut microbiome

In their investigation, the researchers in the current study evaluated data from participants who volunteered for studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University.

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These participants were cognitively normal and provided stool, blood and cerebrospinal fluid (CSF) samples for study along with food diaries. They also underwent brain imaging, including positron emission tomography (PET) and magnetic resonance imaging (MRI) scans, to identify those with signs of preclinical AD.

Of the 164 participants in the study, they found 49 with signs of preclinical AD.

Gut microbiome analysis revealed that, despite eating similar diets, healthy participants and those with preclinical AD had marked differences in the bacterial species present in their gut as well as differences in the biological processes these bacteria were involved in.

The microbiome findings also correlated with the participants’ amyloid and tau levels, which rise before cognitive symptoms appear. However, they did not correlate with neurodegeneration, which usually appears alongside cognitive decline.

“By the time people have cognitive symptoms, there are significant changes that are often irreversible,” said Prof. Beau M. Ances, co-senior author of the study and professor of neurology. “But if you can [diagnose] someone very early in the disease process, that would be the optimal time to effectively intervene with a therapy.”

Potential as an AD screening tool

A five-year follow-up study has now been launched, designed to determine if these gut microbiome changes are a cause or a result of brain changes in preclinical AD.

“If there is a causative link, most likely the link would be inflammatory,” said Prof. Gautam Dantas, co-senior author of the study and a professor of pathology and immunology. “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. 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 [AD].”

“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 Dantas. “It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to Alzheimer’s disease, in which case altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease.”

Overall, the findings of the study open up the possibility of analyzing the gut microbiome to screen and identify people at higher risk of AD, as well as designing preventive treatments to modify the microbiome in the hopes of staving off cognitive decline.

“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” said Ances. “One day individuals may be able to provide a stool sample and find out if they are at increased risk for developing [AD]. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps.”

Reference: Ferreiro AL, Choi J, Ryou J, et al. Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease. Sci. Transl. Med. 2023;15(700):eabo2984. doi: 10.1126/scitranslmed.abo2984

This article is a rework of a press release issued by Washington University School of Medicine in St. Louis. Material has been edited for length and content.