Study finds gut bacteria are altered before Alzheimer’s symptoms show
Results could point toward an easier-to-use diagnostic tool, researchers suggest
In the earliest stages of Alzheimer’s disease, even before cognitive symptoms have become apparent, there are detectable changes in the makeup of bacteria in the gut, a study shows.
The finding suggests that analyses of gut bacteria may help identify early Alzheimer’s, according to researchers.
“By the time people have cognitive symptoms, there are significant changes that are often irreversible. But if you can diagnosis [sic] someone very early in the disease process, that would be the optimal time to effectively intervene with a therapy,” Beau Ances, MD, PhD, a co-corresponding author of the study at Washington University School of Medicine in St. Louis, said in a press release.
“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Ances added. “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 study, “Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease,” was published in Science Translational Medicine.
The human digestive tract is home to billions of bacteria and other microorganisms, collectively known as the gut microbiome. These microscopic tenants of the digestive system play crucial roles in maintaining human health, and emerging studies have shown they may become dysregulated in Alzheimer’s and other neurodegenerative disorders.
Within the brain, Alzheimer’s is marked by the accumulation of toxic clumps of the amyloid-beta protein. However, amyloid-beta accumulation can also be detectable in some people who don’t have any symptoms of Alzheimer’s.
It’s thought that this symptomless amyloid-beta accumulation may represent an early, preclinical stage of Alzheimer’s in which the disease-driving biological processes have begun, but they have not advanced enough to cause noticeable problems.
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.
While gut microbiome changes have been reported in people with symptomatic Alzheimer’s relative to healthy people, whether these changes are present in preclinical stages remains unknown.
To address this, the researchers compared data from stool samples of people with preclinical Alzheimer’s versus those without it.
Study participants and results
The study included 164 people, ages 68 to 94, who did not have any abnormalities on cognitive tests. Data from brain scans and brain and spinal fluid showed that 49 of them (29.9%) had accumulation of amyloid-beta and tau (another protein that forms toxic clumps in Alzheimer’s).
The remaining 115 people (70.1%) did not have signs of such accumulation and were considered healthy. They became the control group.
Patients with preclinical Alzheimer’s tended to be older and weigh less than those in the control group, and fewer of them were Black or had diabetes. However, dietary habits, which can substantially influence the composition of the gut microbiome, were largely comparable between the groups.
Using statistical models to account for the demographic differences, the researchers compared the makeup of the gut microbiome for these patients.
Results showed statistically significant differences in gut microbiome profiles between people with or without preclinical Alzheimer’s. Several species of bacteria — including Dorea formicigenerans, Oscillibacter sp. 57_20, Faecalibacterium prausnitzii, Coprococcus catus, and Anaerostipes hadrus — were present at significantly higher levels in the preclinical Alzheimer’s group.
“These data suggest that the human gut microbiome may change early in [Alzheimer’s], before cognitive impairment becomes apparent,” the researchers wrote.
Other statistical tests showed that the accuracy of identifying preclinical Alzheimer’s patients was increased when gut microbiome data was included in models, compared with models that only used demographic and clinical factors.
Among patients with preclinical Alzheimer’s, those with more gut microbiome dysregulation tended to have higher amyloid-beta and tau levels.
“The association of gut features with the definitive molecular hallmarks of early [Alzheimer’s disease processes] strengthens their potential utility as complementary early-in-progression predictive markers,” the researchers wrote.
Further studies suggested
A limitation of this study, the researchers noted, is that the gut microbiome can change over time, but stool samples were collected just once. As such, they highlighted a need for future studies that sample the gut microbiome at multiple points in time.
The fact that not everyone with preclinical Alzheimer’s will actually develop symptomatic disease in their lifetime also stresses the need for further long-term studies, the team noted.
They also emphasized that while these data suggest that the gut microbiome is dysregulated in the early stages of Alzheimer’s, it’s not clear whether this finding is a cause or consequence of the disease.
“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 Gautam Dantas, PhD, the study’s co-corresponding author at Washington University.
If it turns out that the gut is influencing the brain to help drive Alzheimer’s, it might open the door to new treatment strategies.
“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,” Dantas said.
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