Researchers from Washington University in St. Louis have identified distinctive gut bacteria in individuals in the early stages of Alzheimer’s disease compared to healthy counterparts. This suggests a potential connection between the gut microbiome and dementia, raising the possibility of using gut bacteria to predict or address cognitive decline. The study, involving cognitively normal participants, emphasizes the gut-brain relationship, although it remains uncertain whether changes in the gut lead to brain alterations or vice versa.
The gut microbial composition of those with pre-symptomatic Alzheimer’s varies from that of healthy individuals.
People in the initial phase of Alzheimer’s, where brain changes have begun but cognitive symptoms are not yet evident, display a unique combination of gut bacteria when compared to healthy individuals, according to a research study carried out by the Washington University School of Medicine in St. Louis.
Recently published in the Science Translational Medicine journal, this research suggests the potential for assessing the bacterial makeup of the gut to identify those at a heightened risk of developing dementia. It also introduces the prospect of developing interventions that can modify the microbiome to help deter cognitive deterioration.
Co-corresponding author Gautam Dantas, Ph.D., the Conan Professor of Laboratory and Genomic Medicine, stated, “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. 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.”
The notion of investigating the link between the gut microbiome and Alzheimer’s disease came about during a youth soccer game, where Dantas and Beau M. Ances, MD, Ph.D., the Daniel J. Brennan Professor of Neurology, conversed while their children played. Ances focuses on treating and researching Alzheimer’s disease, while Dantas specializes in the gut microbiome.
While scientists already knew that the gut microbiomes of those with symptomatic Alzheimer’s differ from those of healthy individuals of the same age, Ances conveyed to Dantas that no one had yet studied the gut microbiomes of individuals in the crucial pre-symptomatic phase.
Ances, the other co-corresponding author, mentioned, “By the time people have cognitive symptoms, there are significant changes that are often irreversible. But if you can diagnose someone very early in the disease process, that would be the optimal time to effectively intervene with therapy.”
Throughout the early stage of Alzheimer’s, which can persist for more than two decades, individuals affected accumulate protein clumps of amyloid beta and tau in their brains, yet do not display signs of cognitive decline or neurodegeneration.
Dantas, Ances, and first author Aura L. Ferreiro, Ph.D., initially a graduate student in Dantas’ laboratory and now a postdoctoral researcher, evaluated participants who volunteered for studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University. All participants were cognitively healthy. As part of the study, participants submitted stool, blood, and cerebrospinal fluid samples, maintained food diaries, and underwent PET and MRI brain scans.
To distinguish between those already in the early phase of Alzheimer’s and those who were healthy, the researchers searched for signs of amyloid beta and tau accumulation through brain scans and cerebrospinal fluid analysis. Out of the 164 participants, approximately a third (49) displayed signs of early Alzheimer’s.
An analysis revealed substantial differences in gut bacteria between healthy individuals and those with preclinical Alzheimer’s disease, including variations in the bacterial species present and their involvement in biological processes, despite both groups consuming similar diets. These differences correlated with levels of amyloid and tau, which rise before cognitive symptoms emerge, but did not correlate with neurodegeneration, which becomes evident around the time cognitive abilities begin to decline. These distinctions could potentially be employed to screen for early-stage Alzheimer’s disease, according to the researchers.
Ances commented, “The nice thing about using the gut microbiome as a screening tool is its simplicity and ease. 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.”
The researchers have initiated a five-year follow-up study aimed at determining whether the variations in the gut microbiome are a cause or a consequence of the brain changes observed in early Alzheimer’s disease.
Dantas, also a professor of pathology & immunology, biomedical engineering, molecular microbiology, and pediatrics, noted, “If there is a causative link, most likely the link would 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. 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.”
Source: “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
Funding for the study was provided by the Infectious Diseases Society of America, the National Institute on Aging, Daniel J. Brennan, MD, Fund, and the Paula and Rodger Riney Fund.
Table of Contents
Frequently Asked Questions (FAQs) about Alzheimer’s microbiome
What did the researchers at Washington University discover regarding Alzheimer’s and gut bacteria?
Researchers at Washington University found that individuals in the early stages of Alzheimer’s disease have distinct gut bacteria compared to healthy peers. This suggests a potential link between the gut microbiome and the disease, possibly providing predictive insights or treatment options.
What was the focus of the study conducted by Washington University?
The study conducted by Washington University aimed to investigate the connection between the gut microbiome and Alzheimer’s disease. Specifically, it explored the differences in gut bacteria between individuals in the pre-symptomatic phase of the disease and healthy individuals.
What did the study reveal about gut bacteria in pre-symptomatic Alzheimer’s individuals?
The study revealed that individuals in the early phase of Alzheimer’s, before cognitive symptoms become apparent, exhibit a unique mix of gut bacteria compared to healthy individuals. This suggests that the composition of gut bacteria could potentially serve as an indicator of preclinical Alzheimer’s disease.
Could gut bacteria be used to predict the risk of dementia?
Yes, the research suggests that the composition of gut bacteria might be used as a screening tool to identify individuals at an increased risk of developing Alzheimer’s disease. The distinct differences in gut bacterial composition correlated with the levels of certain proteins associated with the disease, offering potential predictive value.
How could the findings of this study impact future treatments?
The study introduces the possibility of using interventions that modify the gut microbiome to help prevent cognitive deterioration in Alzheimer’s disease. If a causal link between the gut microbiome and Alzheimer’s is established, it could open up avenues for treatments that target gut bacteria to slow down or even halt the progression of symptomatic Alzheimer’s.
What remains uncertain despite the study’s findings?
The study raises questions about the direction of influence between the gut and the brain. It is still unclear whether changes in the gut microbiome lead to brain alterations or if brain changes affect the gut. Further research is needed to determine the exact nature of this relationship.
What is the significance of studying gut bacteria in the pre-symptomatic phase?
Studying gut bacteria in the pre-symptomatic phase of Alzheimer’s is crucial because it offers a window of opportunity for early intervention. Detecting changes in the gut microbiome before cognitive symptoms appear could allow for more effective therapeutic interventions to slow down the progression of the disease.
What additional research is being planned following this study?
The researchers are launching a five-year follow-up study to investigate whether the differences in gut microbiome composition are a cause or a result of the brain changes observed in early Alzheimer’s disease. This could help clarify the relationship between gut bacteria and the progression of the disease.
More about Alzheimer’s microbiome
- Washington University School of Medicine Newsroom
- Science Translational Medicine Journal
- Infectious Diseases Society of America
- National Institute on Aging
- Daniel J. Brennan, MD, Fund
- Paula and Rodger Riney Fund
