What is already known on this topic
About 50 million people worldwide have dementia, with Alzheimer’s disease accounting for up to 70% of total cases of dementia. But although there’s growing evidence that links the gut microbiota to Alzheimer’s disease, the work of characterizing important microbes is still in its infancy.

What this research adds
Researchers analyzed the gut microbiota and the cognitive abilities of healthy people and individuals with mild cognitive impairment and Alzheimer’s disease. They found that the levels of Faecalibacterium prausnitzii were lower in people with mild cognitive impairment compared to healthy people. Transferring two F. prausnitzii strains from healthy individuals to a mouse model of Alzheimer’s disease improved the mice’s cognitive difficulties.

Conclusions
The findings suggest that some F. prausnitzii strains could be good candidates for microbiota-based therapies against Alzheimer’s disease.

About 50 million people worldwide have dementia, with Alzheimer’s disease accounting for up to 70% of total cases of dementia. New research in mice shows that some gut microbes may help ease the cognitive difficulties associated with Alzheimer’s disease.

The findings, published in Cell Reports Medicine, suggest that specific strains of the gut commensal Faecalibacterium prausnitzii could be good candidates for microbiota-based therapies against Alzheimer’s.

Several studies have linked the gut microbiota to brain conditions including autism, Parkinson’s disease and Alzheimer’s disease. For example, antibiotic treatments have been shown to decrease amyloid-beta plaque deposition in a mouse model of Alzheimer’s, and several studies in people have reported a relationship between the gut microbiota and Alzheimer’s disease or mild cognitive impairment, a condition that precedes Alzheimer’s.

However, the work of characterizing important microbes is still in its infancy. To investigate whether there is a causal relationship between specific gut bacteria and cognitive difficulties, Takuji Yamada at Tokyo Institute of Technology and his colleagues analyzed the microbiota and the cognitive abilities of healthy people and individuals with mild cognitive impairment and Alzheimer’s disease.

Microbial imbalance

The researchers recruited 21 healthy people, 15 individuals with mild cognitive impairment and seven individuals with Alzheimer’s disease. All individuals lived in Japan and those with cognitive difficulties or dementia were 65 years or older. 

The abundances of six types of bacteria were different between healthy people and those with mild cognitive impairment. In particular, bacteria such as Faecalibacterium, Ruminococcaceae and Anaerostipes were decreased in people with mild cognitive impairment, whereas Prevotella bacteria were increased, compared with healthy individuals.

The team also found bacteria that were more abundant in healthy people and whose abundance correlated with cognitive scores. Among these bacteria, F. prausnitzii was the most abundant in healthy people and was decreased substantially in individuals with mild cognitive impairment.

Cognitive improvement

After isolating two F. prausnitzii strains from healthy individuals, the researchers transferred the bacteria to a mouse model of Alzheimer’s and measured the mice’s cognitive skills. Both strains improved the cognitive impairment associated with Alzheimer’s, the researchers found. 

To explore the potential mechanism of action of F. prausnitzii in the brain, the team analyzed the metabolites in the mice’s hippocampus, a brain region involved in memory. One of the F. prausnitzii strains reduced the levels of several metabolites, including some that have been implicated in oxidative stress and mitochondrial function. 

More research is needed to determine whether the differences in the abundances of Faecalibacterium between healthy people and those with mild cognitive impairment are a universal phenomenon, the researchers say. Future studies should also investigate the efficacy of F. prausnitzii strains on the build-up of amyloid-beta plaques in the brain of mouse models of Alzheimer’s, the authors add.