Neuroscientists from The University of Chicago find that treating mice with broad-spectrum antibiotics long term decreases plaques that cause Alzheimer's disease and elevate the inflammatory state of microglial cells in the brain.

Plaques, or clusters, of a protein called beta-amyloid - along with the inflammation surrounding these plaques - play a significant role in the development of Alzheimer's disease (AD).

It is suggested that amyloidosis - the accumulation and buildup of beta-amyloid peptides into plaques in the brain - is key to AD onset and progression.

Inflammation of the microglia, brain cells that perform immune system functions in the central nervous system, and the severity of that neuroinflammation may affect the rate of cognitive decline from AD.

In addition to decreasing amyloid plaques and activating inflammatory microglial cells in the brain, the study, published in Scientific Reports, showed that administering antibiotics made significant changes in the gut microbiome of the mice.

The gut microbiome changes indicate that that the composition and diversity of gut bacteria could be fundamental in regulating immune system activity that influences AD progression.

"We're exploring very new territory in how the gut influences brain health," says senior author Sangram Sisodia, Ph.D., a Thomas Reynolds Sr. Family professor of neurosciences at The University of Chicago.

"This is an area that people who work with neurodegenerative diseases are going to be increasingly interested in, because it could have an influence down the road on treatments."

Beta-amyloid plaques reduced by twice the amount with antibiotics
Sisodia and colleagues conducted the study by giving mice high doses of broad-spectrum antibiotics over a 5-6-month period.

Gut bacteria from the mice treated with antibiotics were examined. Genetic analysis showed that while the quantity of microbes present in the gut was similar to the controls', the diversity of the microbes were noticeably different.

Compared with the controls, the antibiotic-treated mice experienced more than a twofold decrease in beta-amyloid plaques. There was an elevation in both the inflammatory status of microglia in the brain and signaling chemicals that circulate in the blood.

Although the link between these discoveries is uncertain, future studies could focus on how the gut microbiome affects the brain and nervous system.

Understanding gut bacteria changes could lead to personalized medicine
"We don't propose that a long-term course of antibiotics is going to be a treatment - that's just absurd for a whole number of reasons," says lead author Myles Minter, Ph.D., a postdoctoral scholar in the Department of Neurobiology at The University of Chicago.

"But what this study does is allow us to explore further, now that we're clearly changing the gut microbial population and have new bugs that are more prevalent in mice with altered amyloid deposition after antibiotics," he adds.

The study was led by the Microbiome Centre - a collaboration between The University of Chicago, the Marine Biological Laboratory, and Argonne National Laboratory - to coordinate research across different fields to increase understanding of the microbiome.

"Once you put ideas together from different fields that have largely long been believed to be segregated from one another, the possibilities are really amazing," notes Minter.

"There's probably not going to be a cure for Alzheimer's disease for several generations, because we know there are changes occurring in the brain and central nervous system 15-20 years before clinical onset," says Sisodia.