Altered Gut Bacteria a Biomarker of Preclinical Alzheimer's?

Megan Brooks

June 16, 2023

The composition of gut bacteria in people with preclinical Alzheimer's disease (AD) differs from that of healthy people, a new study shows.

The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers note.

Study investigator Gautam Dantas, PhD, cautioned that it's not known 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 AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease," Dantas, with Washington University School of Medicine in St. Louis, said in a news release.

The study was published online June 14 in Science Translational Medicine.

Stool Test?

Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.

To investigate, Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.

After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.

The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, "suggesting that the gut microbial community changes early in the disease process," the researchers suggest.

The researchers also identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.

The findings suggest "markers in the stool might complement early screening measures for preclinical AD," the researchers note.

"The nice thing about using the gut microbiome as a screening tool is its simplicity and ease," Beau Ances, MD, PhD, professor of neurology, at Washington University in St. Louis, said in the release.

"One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. 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," Ances added.

The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.

Caveats, Cautionary Notes

Commenting on this study for Medscape Medical News, Claire Sexton, DPhil, Alzheimer's Association senior director of scientific programs and outreach, cautioned that the study design means that it's "not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research."

Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, "it's still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer's."

Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.

"If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings," Sexton said.

This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Riney Fund. Dantas, Ances and Sexton have no relevant disclosures.

Sci Transl Med. Published online June 14, 2023. Full text

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