Ones with pre-symptomatic Alzheimer's have different gut flora than healthy ones


A study by the Washington University School of Medicine in St. Louis found that persons in the early stages of Alzheimer's disease, when brain changes have begun but before cognitive symptoms are noticeable, had a unique combination of gut flora compared to healthy individuals.

This study, which was just published in the journal Science Translational Medicine, raises the possibility of identifying people with a higher risk of dementia by looking at the bacterial composition of their guts. It also raises the possibility of developing drugs that alter the microbiome to help stop cognitive decline.

However, it is important to know this link regardless of whether the gut influences the brain or the brain influences the gut, according to co-corresponding author Gautam Dantas, Ph.D., the Conan Professor of Laboratory and Genomic Medicine. It's possible that alterations in the gut microbiota are only a sign of pathological brain changes. Altering the gut microbiota with probiotics or fecal transplants may help slow the progression of the disease if the gut microbiome is implicated in the development of Alzheimer's disease.

When Dantas and Beau M. Ances, MD, Ph.D., the Daniel J. Brennan Professor of Neurology, were chatting while their kids played soccer, they had the idea to research the link between the gut flora and Alzheimer's disease. Dantas is an authority on the gut microbiota, while Ances treats and researches Alzheimer's patients.

Scientists were already aware that the gut microbiomes of individuals with symptomatic Alzheimer's disease were different from those of age-matched healthy individuals. Ances, however, informed Dantas that no one had yet examined the gut microbiomes of individuals in the crucial pre-symptomatic stage.

According to Ances, the second co-corresponding author, "there are major alterations that are frequently irreversible by the time people develop cognitive symptoms. But the best opportunity to properly act with a therapy is if you can diagnose someone extremely early in the course of the disease.

Affected individuals develop clumps of the proteins amyloid beta and tau in their brains throughout the early stages of Alzheimer's disease, which can endure for at least two decades, but do not show symptoms of neurodegeneration or cognitive loss.

Participants who volunteered for studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University were examined by Dantas, Ances, and first author Aura L. Ferreiro, Ph.D., who was a graduate student in Dantas' lab at the time and is now a postdoctoral researcher. Cognitively, each subject was in the range. Participants in this study kept dietary diaries, supplied stool, blood, and cerebrospinal fluid samples, and underwent PET and MRI brain scans.

Through brain imaging and cerebrospinal fluid analysis, the researchers searched for indicators of amyloid beta and tau accumulation to separate patients with early-stage Alzheimer's disease from those who were healthy. A third (49) of the 164 participants had early Alzheimer's symptoms.

According to an analysis, despite eating essentially the same food, those with preclinical Alzheimer's disease and those who are healthy have very different gut bacteria in terms of the bacterial species present and the biological processes those bacteria are involved in. These variations did not correspond with neurodegeneration, which becomes apparent around the time cognitive abilities begin to diminish, but did correlate with amyloid and tau levels, which grow before cognitive symptoms manifest. The researchers suggested that these variations might be utilized to screen for early Alzheimer's disease.

The accessibility and simplicity of employing the gut microbiome as a screening tool is wonderful, according to Ances. In the future, people might be able to submit a sample of their faeces to determine whether they have a higher chance of getting Alzheimer's disease. Compared to brain scans or spinal taps, it would be significantly simpler, less invasive, and more accessible for a huge section of the population, especially underrepresented groups.

To determine whether the abnormalities in the gut microbiome are a cause or an effect of the brain changes identified in early Alzheimer's disease, the researchers have started a five-year follow-up study.

According to Dantas, a professor of pathology & immunology, biomedical engineering, molecular microbiology, and pediatrics, if there is a causal link, it is most likely an inflammatory one. Bacteria are these incredible chemical factories, and some of their metabolites have an impact on gut inflammation or even travel via the bloodstream to affect the immune system throughout the body. At this moment, everything is hypothetical, but if it turns out that there is a causal relationship, we can begin to consider whether encouraging "good" bacteria or eliminating "bad" bacteria could delay or even prevent the onset of symptomatic Alzheimer's disease.



Reference: “Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease” by Aura L. Ferreiro, JooHee Choi, Jian Ryou, Erin P. Newcomer, Regina Thompson, Rebecca M. Bollinger, Carla Hall-Moore, I. Malick Ndao, Laurie Sax, Tammie L. S. Benzinger, Susan L. Stark, David M. Holtzman, Anne M. Fagan, Suzanne E. Schindler, Carlos Cruchaga, Omar H. Butt, John C. Morris, Phillip I. Tarr, Beau M. Ances and Gautam Dantas, 14 June 2023, Science Translational Medicine.
DOI: 10.1126/scitranslmed.abo2984


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