Uncovering the link between the gut microbiome and neurodegeneration could lead to new treatment modalities. [wildpixel/Getty Images]
Uncovering the link between the gut microbiome and neurodegeneration could lead to new treatment modalities. [wildpixel/Getty Images]

The association between the human microbiome and overall general health becomes stronger with each passing day. Specifically, evidence uncovering the influence gut microbiota exert on seemingly disparate biological pathways, such as the brain and nervous system, has become an exciting area of scientific study. Now researchers at the University of Chicago (UChicago) have published new findings that show long-term treatment with broad-spectrum antibiotics decreased levels of amyloid plaques—a hallmark of Alzheimer's disease (AD)—and activated inflammatory microglial cells in the brains of mice.        

The new study, published today in Scientific Reports in an article entitled “Antibiotic-Induced Perturbations in Gut Microbial Diversity Influences Neuro-Inflammation and Amyloidosis in a Murine Model of Alzheimer's Disease,” also showed significant changes in the gut microbiome after antibiotic treatment, suggesting the composition and diversity of bacteria in the gut play an important role in regulating immune system activity that impacts progression of AD.

“We're exploring very new territory in how the gut influences brain health,” explained senior study author Sangram Sisodia, Ph.D., professor of neurosciences at UChicago. “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.”

Two important symptoms of AD are the development and progression of amyloidosis, which is the accumulation of amyloid-ß (Aß) peptides in the brain, as well as inflammation of the microglia, brain cells that perform immune system functions in the central nervous system. The accumulation of Aß into plaques plays a pivotal role in the onset of AD, whereas the severity of neuro-inflammation has been associated with influencing the rate of cognitive decline from the disease.

The UChicago team administered high doses of broad-spectrum antibiotics to mice over 5 to 6 months. At the end of this period, genetic analysis of gut bacteria from the antibiotics-treated mice showed that although the total mass of microbes present was roughly the same as in controls, the diversity of the community changed dramatically. 

Remarkably, the antibiotics-treated mice showed more than a two-fold decrease in Aß plaques compared to controls and a significant elevation in the inflammatory state of microglia in the brain. Levels of important signaling chemicals circulating in the blood were also elevated in the treated mice.

Although the mechanisms linking these changes are unclear, the researchers stressed that further research on the gut microbiome's influence on the brain and nervous system could potentially open the door toward new treatment modalities—just not directly using antibiotics.

“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,” noted lead study author Myles Minter, Ph.D., a postdoctoral scholar in the department of neurobiology at UChicago. “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.”

Moreover, while the investigators were excited by their findings and recognized that they could open new possibilities for understanding the role of the gut microbiome in AD, they cautioned not to overinterpret the results as the study is just the initial step.

“There's probably not going to be a cure for AD for several generations because we know there are changes occurring in the brain and central nervous system 15 to 20 years before clinical onset,” Dr. Sisodia remarked. “We have to find ways to intervene when a patient starts showing clinical signs, and if we learn how changes in gut bacteria affect onset or progression, or how the molecules they produce interact with the nervous system, we could use that to create a new kind of personalized medicine.”