Transplanting Microbiota From Alzheimer’s Patients Leads to Changes in Brain Function
Post by Anastasia Sares
The takeaway
The need to understand Alzheimer’s disease is becoming more urgent. This work establishes a causal role for changes to the gut microbiome in the development of Alzheimer’s.
What's the science?
The microbes living in our intestinal tract can produce compounds that either affect our body directly or are important precursors for the body’s functions. Studies have noted a correlation between Alzheimer’s disease and gut health, but this correlation is not enough to say with confidence that poor gut health actually contributes to Alzheimer’s disease. For that, a real experiment is needed. This week in Brain, Grabrucker, Marizzoni, Silajžić and colleagues transplanted fecal samples from people with and without Alzheimer’s into rats, which led to changes in their brain development and cognitive function.
How did they do it?
In order to show that gut bacterial composition caused changes in brain health, the authors took samples of human fecal matter from older adults with and without Alzheimer’s-type dementia and transplanted it into rats with a depleted microbiome (the depleted microbiome was achieved by giving the rats a cocktail of antibiotics before the fecal transplant). In essence, this procedure replaced a significant amount of the rats’ original gut bacteria with that of the human participants. In this way, rats were randomly subjected to “healthy” or “unhealthy” gut bacteria, and the authors could then measure the effects on the brain.
The rats were examined for changes in brain structure and function. Measures of brain structure included how many new neurons were generated in the hippocampus and the branching patterns of these new neurons. Measures of brain function included the ability to complete a maze and the ability to recognize and explore novel objects.
What did they find?
The human participants with Alzheimer’s disease had signs of inflammation in blood and fecal samples. Their microbiomes were also abnormal, with an increase in bacterial species that are thought to cause inflammation and pathology (Bacteriodetes and Desulfovibrio) and a decrease in species that are thought to produce beneficial compounds (Fimicutes, Verruocomicrobiota, Clostridium sensu stricto 1, and Coprococcus). Several of these microbial differences were observed in the rats who received the fecal transplants as well, along with alterations in the colon for the rats who received transplants from humans with Alzheimer’s (more fecal water content, fewer goblet cells, and a reduction in colon length). Not only that, but the rats with the Alzheimer’s microbiota performed worse on cognitive tests, like distinguishing between new and familiar objects or remembering where to go in a water maze. These rats also had fewer new neurons in their hippocampi at the end of the 50-day period, and these neurons had less complex branching structures.
What's the impact?
This work supports the idea of a causal role of gut health in the development of Alzheimer’s disease, which may lead to interventions that focus on gut health as a protective factor for the disease. This work also highlights how animal research can bring high-value insights, by uncovering new avenues for therapeutic approaches to devastating diseases like Alzheimer’s disease.