A compound found in the gut may reduce some of the manifestations of Alzheimer’s disease, according to a Northwestern Medicine study published in the Journal of Clinical Investigation.
Alzheimer’s disease, the most common form of dementia, impacts more than 6 million Americans. That number is expected to rise dramatically as the population ages, according to the Alzheimer’s Association.
While mounting evidence has pointed to a connection between the gut microbiome and the degenerative effects of Alzheimer’s disease, the mechanisms are not well understood, said Robert Vassar, PhD, the Davee Professor of Alzheimer Research and professor of Neurology and director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, who was senior author of the study.
“There are differences in Alzheimer’s patients and their gut microbiota, and that’s been verified by many groups now,” Vassar said. “Prior research has shown that when you make changes in the gut microbiota of Alzheimer model mice, you in turn have effects on the pathology of the hallmarks of Alzheimer’s – amyloid plaques and tau accumulation– suggesting that there’s a cause and effect.”
In the study, Vassar and his collaborators studied mice with Alzheimer’s disease that were treated with antibiotics known to alter the gut microbiome. They found that mice treated with antibiotics showed an increase in a short-chain fatty acid known as propionate, produced by certain species of bacteria in the gut.
Propionate plays a crucial role in regulating brain inflammation and amyloid plaque buildup — two key features of the devastating neurodegenerative condition.
Investigators then added propionate to the mice’s drinking water. They found that mice with higher levels of the compound had reduced inflammation and toxic plaques, according to the findings. Additionally, treated mice had lower levels of IL-17, a pro-inflammatory cytokine involved in the body’s defense against infections.
However, the effects were significant only in male mice.
“We think that the antibiotics were changing the composition of the gut microbiota and specifically increasing the bacteria Akkermansia, which produces propionate,” Vassar said. “Mice treated with propionate in the drinking water had fewer of the reactive astrocytes and the amyloid plaques.”
The findings suggest that boosting propionate levels — whether through diet, probiotics or medication — may help slow the progression of Alzheimer’s, Vassar said.
“It’s very exciting that this short-chain fatty acid propionate could be used therapeutically in people for the prevention of Alzheimer’s disease,” Vassar said.
Vassar and his collaborators will now work to understand how female sex hormones impact the gut microbiome and responses to antibiotic treatment, he said. His team will also pursue further studies to understand the role of IL-17 in Alzheimer’s progression.
“Our hypothesis is that propionate released from the gut gets into the blood, and it lowers IL-17. But why is that protective?” Vassar said. “We don’t know the answer to that yet, but we envision more mechanistic studies in the mice to help us sort out what the mechanism is. That’s also important for translational work to get our findings into the clinic to help patients.”
Sidhanth Chandra, a student in the Medical Scientist Training Program (MSTP), was first author of the study.
The study was supported by Open Philanthropy/Good Ventures Foundation, Cure Alzheimer’s Fund and the Luminescence Foundation.
