Altered gut bacteria could be early warning sign of Alzheimer’s

Gut microbes found in people with pre-symptomatic Alzheimer’s disease could pave the way for diagnostic advancements.

A new study conducted by researchers at Washington University School of Medicine in St Louis has explored the composition of gut bacteria in individuals in the earliest stage of Alzheimer’s disease. The research, which is published in Science Translational Medicine, not only identifies potential indicators of heightened dementia risk, but also offers prospects for developing microbiome-altering preventive treatments to combat cognitive decline.

Longevity.Technology: Previously, science has noted differences in the gut microbiomes of individuals with symptomatic Alzheimer’s compared with their healthy counterparts. However, the current study delves deeper, focusing on the gut microbiomes of individuals in the crucial pre-symptomatic phase. During this phase, individuals accumulate amyloid beta and tau proteins in their brains without exhibiting neurodegeneration or cognitive decline, which can persist for over two decades. Earlier diagnosis would enable people to access support and resources, plan for the future and well as onboarding treatments that could slow the progression of the disease. An idea of future numbers of patients would also allow health care infrastructure to be better prepared.

The researchers evaluated participants who volunteered at the Charles F and Joanne Knight Alzheimer Disease Research Center at Washington University, specifically selecting cognitively normal individuals. These participants provided samples of stool, blood, and cerebrospinal fluid, recorded their dietary habits, and underwent PET and MRI brain scans.

To differentiate between individuals in the early stage of Alzheimer’s disease and healthy individuals, the researchers employed brain scans and cerebrospinal fluid analysis to identify signs of amyloid beta and tau accumulation. Out of the 164 participants, approximately one-third (49) exhibited indications of early Alzheimer’s [1].

The analysis unveiled distinct differences in gut bacteria between healthy individuals and those in the preclinical phase of Alzheimer’s disease, notwithstanding similar dietary habits. These differences encompassed both the species of bacteria present and the underlying biological processes in which these bacteria participate.

“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, PhD, the Conan Professor of Laboratory and Genomic Medicine. “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 [2].”

Strikingly, the differences uncovered by the research correlated with the levels of amyloid beta and tau, which rise before cognitive symptoms manifest. However, they did not correspond with neurodegeneration, which typically becomes noticeable when cognitive abilities begin to decline. These findings hold promise for the potential screening of early Alzheimer’s disease using gut bacteria composition as an indicator.

“By the time people have cognitive symptoms, there are significant changes that are often irreversible,” said co-corresponding author Beau M Ances, MD, PhD, the Daniel J Brennan Professor of Neurology. “But if you can diagnosis someone very early in the disease process, that would be the optimal time to effectively intervene with a therapy [2].”

Building upon these findings, the researchers have now initiated a five-year follow-up study aimed at elucidating whether the differences observed in the gut microbiome are a cause or consequence of the brain changes associated with early Alzheimer’s disease. This crucial investigation will shed further light on the complex relationship between the gut microbiome and the development of Alzheimer’s, potentially leading to novel therapeutic interventions and diagnostic tools.

“If there is a causative link, most likely the link would be inflammatory,” said Dantas. “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 Alzheimer’s disease [2].”

By highlighting the distinctive composition of gut bacteria in individuals with preclinical Alzheimer’s disease, this study could well provide a valuable avenue for early detection strategies. Leveraging these findings could pave the way for quick, speedy diagnostics, personalized interventions and improved outcomes for individuals at risk of cognitive decline.

“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Ances said. “One day individuals may be able to provide a stool sample and find out if they are at increased risk for developing Alzheimer’s disease. 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 [2].”

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