Gut microbiota composition may warn of early Alzheimer’s disease

The results of a human study by researchers at the Washington University School of Medicine in St. Louis show that the gut in the early stages of Alzheimer’s disease (AD)—the stage when brain changes have already begun but before cognitive symptoms become apparent. suggesting microbiome composition. – It is different from that of a healthy person. The research team’s work identifies specific gut types associated with preclinical Alzheimer’s disease and improves the accuracy of machine learning classifiers to predict preclinical Alzheimer’s disease status by including such microbiome features. can be improved.

Overall study results suggest that it may be feasible to analyze an individual’s gut microbiome to identify those at increased risk of developing dementia, and may reverse cognitive decline It also points to the possibility of designing preventive treatments that alter certain microbiota.

“We don’t yet know whether the gut influences the brain or the brain influences the gut, but in either case, knowing this connection is valuable,” says Conan’s experiment Genomics. Professor of Medicine Dr Gautam Dantas said. “Changes in the gut microbiome may just be reading pathological changes in the brain. Another option is that the gut microbiome contributes to Alzheimer’s disease.” In that case, altering the gut microbiome through probiotics or faecal import may help alter the course of the disease,” Dantas said in a paper published by the team in 2016. Co-correspondent author. scientific translational medicinetitled “Gut microbiota composition may be an indicator of preclinical Alzheimer’s disease“Correlations between preclinical Alzheimer’s disease neuropathology and the gut microbiome may improve our understanding of the pathogenesis of Alzheimer’s disease,” the researchers said in their report. It may help identify the

The human gut microbiome contains a “compositionally and functionally diverse microbial community” that influences health and well-being, the authors noted. “These communities, he said, contain more than 1012 bacterial cells, representing thousands of taxa that encode a vast repertoire of pathways that diversely affect human physiology and metabolism. .”

The idea to study the relationship between the gut microbiome and Alzheimer’s disease came about when Dantas and co-author Daniel J. Brennan Neurology Professor Bo M. Anthes, M.D., chatted sideways to children. I got the idea at a youth soccer game. played. Anthes treats and researches people with Alzheimer’s disease. Dantas is a gut microbiome expert.

Scientists already know that the gut microbiome of people with symptomatic Alzheimer’s disease is different from that of healthy people of the same age. “Several lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis,” the authors further commented. But Anthes told Dantas that no one has yet examined the gut microbiome of people in the critical presymptomatic stage. “…there is limited knowledge about changes in the gut microbiota prior to the onset of symptomatic Alzheimer’s disease,” the researchers write in their paper.

“By the time people show cognitive symptoms, significant and often irreversible changes have occurred. But if we can diagnose someone very early in the disease process, it can effectively intervene in treatment.” It will be the right time,” said Anthes. ”

In the early stages of Alzheimer’s disease, which can last more than 20 years, clumps of proteins called amyloid-beta and tau begin to build up in the brain, but affected people still show no signs of neurodegeneration or cognitive decline. “Substantial data suggest that there is an interval of at least 10 years between initial Aβ plaque deposition in the brain and the first clinical signs of dysfunction,” the researchers noted. “Early detection of the molecular hallmarks of AD pathology remains critical to implementing effective treatments.”

About the newly reported study, Dantas and Ances, and lead author Orla L. Ferreiro, Ph.D., then a graduate student and now postdoctoral fellow in Dantas’ lab, said that Charles F. and Joan Knight Alzheimer’s disease Participants who volunteered to participate in research at the center were evaluated. A research center at the University of Washington. All study participants had normal cognitive abilities. They provided stool, blood, and cerebrospinal fluid samples, kept food diaries, and underwent tests such as PET and MRI brain scans.

To distinguish healthy participants from those already in the early stages of Alzheimer’s disease, the researchers looked for signs of amyloid-beta and tau accumulation through brain scans and cerebrospinal fluid. Of the 164 participants, 49 had signs of early Alzheimer’s disease.

Their analysis showed that healthy and preclinical Alzheimer’s disease patients, despite eating essentially the same diet, differ in terms of the types of bacteria present and the biological processes in which those bacteria are involved. It became clear that they possess remarkably different intestinal bacteria. “The preclinical stage of Alzheimer’s disease revealed different microbiome compositions and functional potentials of microbes,” the scientists said.

These differences could be used to screen for early Alzheimer’s disease, the researchers said. “The association of intestinal features with definitive molecular features of early Alzheimer’s disease reinforces their potential utility as complementary early-stage predictive biomarkers…Faecal microbiome markers may be useful in preclinical studies.” It may complement early screening tools for Alzheimer’s disease and generate promising hypotheses about the potential role of the intestinal tract.” Gut condition in the progression of Alzheimer’s disease. ”

For certain predictive computational models, including taxonomic features of the microbiome improved average accuracy by more than 11% and specificity by more than 27%. “Characterization of the gut microbiome may enhance early screening tools to identify candidates for follow-up CSF or PET Aβ assays to validate preclinical Alzheimer’s disease status,” the researchers further suggested. bottom.

Anthes added, “The advantage of using the gut microbiome as a screening tool is its simplicity and ease. One day, individuals will provide stool samples to learn if they have an increased risk of developing Alzheimer’s disease.” It would be much easier, less invasive, and more accessible to a large portion of the population, especially an underrepresented group, than a brain scan or spinal tap.”

The authors further add, “Overall, the associations reported in this study between the gut microbiome and preclinical AD status or AD markers support the presence of a gut neuroimmune axis in neurodegenerative diseases.” concluded. Here we report that such associations have been established in preclinical Alzheimer’s disease, and that at least some of these microbial species may be causally located. They tested the association in more patients with preclinical Alzheimer’s disease, assessed causality, and whether the association extends to symptomatic Alzheimer’s disease or whether the association extends to other gut microbiomes. He noted that more research is needed to determine whether immune traits associated with Alzheimer’s disease are inherited. disease progression. ”

Researchers have launched a five-year follow-up study aimed at figuring out whether differences in the gut microbiome are a cause or a consequence of the brain changes seen in early Alzheimer’s disease.

“If there is a causative link, it will most likely be inflammation,” Dantas said. Dr. Dantas is also Professor of Pathology and Immunology, Biomedical Engineering, Molecular Microbiology, and Pediatrics. “Bacteria are amazing chemical factories and some of their metabolites can affect inflammation in the gut and even find their way into the bloodstream, affecting the immune system throughout the body. All of this is speculation, but if it turns out that there is a causal relationship, it may promote the growth of “good bacteria” or eliminate “bad bacteria” to slow the progression of symptoms, or even can start thinking about whether it can be stopped. Alzheimer’s disease. The authors further state that “microbially at-risk populations may open up new opportunities for gut-directed interventions to halt progression to clinical Alzheimer’s disease.”