The role of the gut microbiome in the pathogenesis of Alzheimer’s disease has finally been confirmed.
Using gut microbiome transplantation, an international team of researchers has shown that memory impairment in humans with Alzheimer’s disease can be inherited by young, healthy rats.
The study also found that certain bacteria in the gut are directly linked to cognitive decline in Alzheimer’s patients.
This highlights the gut microbiome as an important area of research in Alzheimer’s disease and other dementias, which could lead to new treatments for the disease.
“Alzheimer’s patients are usually diagnosed at or after the onset of cognitive symptoms, which may be too late, at least with current treatments.” To tell says Yvonne Nolan, a neuroscientist at University College Cork (UCC) in Ireland.
“Understanding the role of gut bacteria in the prodromal or early stages of dementia, before symptoms develop, could pave the way for the development of new treatments and even tailored interventions. .”
Recently, evidence has pointed to changes in the gut microbiome as a potential risk factor for the development of Alzheimer’s disease, but it has not been clear whether they are simply somehow related. It has now been confirmed that the gut microbiome indeed plays a causative role in the development of devastating disease symptoms.
“Alzheimer’s disease is an insidious disease and there is still no effective treatment.” To tell Sandrine Thuret, neuroscientist at King’s College London (KCL). “This study represents an important step forward in our understanding of this disease.”
Mr. Nolan, Mr. Thuret, and colleagues from UCC, KCL, and others. IRCCS cent The John of God Clinical Research Center in Bressi, Italy, set out to understand how the gut microbiome of Alzheimer’s patients influences brain health and behavior.
Human participants, including 69 patients with Alzheimer’s disease and 64 healthy controls, donated blood for the study, and a portion of each group also provided gut microbiota through stool samples.
They transplanted the gut microbiota of Alzheimer’s patients into 16 young adult rats whose microbiomes were depleted for one week with antibiotics. A corresponding group of 16 rats received gut microbiota from a healthy control group of humans.
At least 10 days after implantation, the rats underwent behavioral tests designed to assess memory performance and other traits associated with Alzheimer’s disease.
Rats transplanted with microbiomes from Alzheimer’s patients showed impairments in memory behavior that depend specifically on a process called adult hippocampal neurogenesis.
Hippocampal neurogenesis produces new neurons in the hippocampus. Hippocampusa region of the brain important for memory and mood, and one of the first regions affected by Alzheimer’s disease.
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“The memory test we investigated relies on the growth of new neurons in the hippocampal region of the brain.” explain Nolan. “Animals with the gut bacteria of Alzheimer’s patients produced fewer new nerve cells and had impaired memory.”
Rats with the gut microbiota of Alzheimer’s patients showed more severe impairments in hippocampal neurogenesis when the donor’s own cognitive test scores were lower.
Researchers also found clear changes in the rats’ hippocampus. metabolome – A collection of metabolites, such as amino acids and enzymes, that are involved in cell maintenance, growth, and normal function. These changes may contribute to reduced growth of new neurons in the hippocampus.
Although hippocampal neurogenesis cannot be measured as easily in living humans, blood from Alzheimer’s patients reduced neurogenesis in human neural stem cells in the laboratory.
Gene expression levels in stem cells exposed to the blood of Alzheimer’s patients were also associated with patients’ performance on cognitive tests and the types of bacteria in their guts.
“Impaired neurogenesis may be a converging link between the observed changes in gut microbiota composition and cognitive impairment in Alzheimer’s disease,” the research team said. write.
bacteria of the genus Coprococcus, associated with healthy aging, was significantly reduced in Alzheimer’s disease patients. They also had more bacteria. Desulfovibrio genus, similar than cognitively healthy controls past research In animal models of Alzheimer’s disease and Parkinson’s disease.
The researchers say future studies should thoroughly evaluate other aspects that influence the gut microbiome, such as health status, lifestyle factors, and medication history.
“This collaboration has laid the foundation for future research in this area,” said Touré. To tell“And my hope is that it will lead to potential advances in therapeutic interventions.”
The study was published in the journal brain.
