The gut microbes of people early in Alzheimer's disease, but who do not yet have symptoms, differ from those of healthy people, which could help develop more accurate models to predict Alzheimer's risk.
A study from the University of Washington in Saint Louis (USA), published in Science Translational, adds to the evidence that points to the importance of the intestinal microbiome in the early stages of this disease.
"We don't yet know if the gut influences the brain or if the brain influences the gut, but it is valuable to know this association in either case," said Gautam Dantas, one of the authors of the research.
Changes in the gut microbiota may just be a readout of pathological changes in the brain, Dantas said.
The other alternative is that the microbiome "is contributing to Alzheimer's disease, in which case," he added, "altering the gut microbiome with probiotics or fecal transfers could help change the course of the disease."
However, it is still early to establish a causal relationship between the two factors and further research is needed to develop the connection between the gut microbiome and specific markers of Alzheimer's disease.
The human gut microbiome is a vast and extremely diverse community of organisms that is essential for health, metabolism, and well-being, and its disturbances have been linked to a host of disorders.
The researchers conducted a study of 164 cognitively healthy people with and without preclinical Alzheimer's, defined as the asymptomatic presence of abnormal amyloid and tau proteins in the brain, which are what cause the disease.
Tests were performed to distinguish participants and approximately one third (49) had signs of early-stage Alzheimer's.
One analysis found that healthy people and those with preclinical Alzheimer's disease have markedly different gut bacteria—in terms of the species of bacteria present and the biological processes those bacteria are involved in—despite essentially following the same diet.
People with preclinical Alzheimer's had, for example, a greater presence of the bacterial species Doreaformicigenerans, as well as more active microbial pathways involved in the degradation of the amino acids arginine and ornithine.
These differences in the microbiota were correlated with amyloid and tau levels, which rise before cognitive symptoms appear, but not with neurodegeneration, which becomes apparent around the time cognitive abilities begin to decline.
These differences, according to the researchers, could serve to detect Alzheimer's disease at an early stage, which is the optimal time to intervene with a therapy.
The initial phase of the disease can last two decades or more without cognitive decline, but by the time cognitive symptoms occur, "significant changes have already occurred that are often irreversible," said co-author Beau Ances.
The team has launched a five-year follow-up study designed to find out if differences in the gut microbiome are a cause or a consequence of the brain changes seen in the early stages of Alzheimer's.
"If there is a causal relationship, it is most likely inflammatory," said Dantas, who reiterated that, for the moment, everything is speculative.
If a causal relationship ultimately turns out, "we can start to think about whether promoting the 'good' bacteria or getting rid of the 'bad' ones might slow or even stop the development of symptomatic Alzheimer's disease."
