Researchers at the University of Chicago have demonstrated that the type of bacteria living in the gut can influence the development of Alzheimer’s disease symptoms in mice. The study, which will be published this week in the Journal of Experimental Medicine, shows that, by altering the gut microbiome, long-term antibiotic treatment reduces inflammation and slows the growth of amyloid plaques in the brains of male mice, though the same treatment has no effect on female animals.
The community of bacteria that live in the gastrointestinal tract—the gut microbiome—is generally harmless, but, because they affect the activity of the body’s immune system, these bacteria can influence a wide range of diseases, even in distant tissues such as the brain.
“Recent evidence suggests that intestinal bacteria could play a major role in various neurological conditions including autism spectrum disorders, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease,” explains Sangram S. Sisodia, PhD, director of the Center for Molecular Neurobiology at UChicago.
Alzheimer’s disease is characterized by the formation of amyloid plaques and the activation of immune cells present in the brain known as microglia. These cells can help remove amyloid plaques, but their activation may also exacerbate the disease by causing neuroinflammation.
Alzheimer’s patients exhibit changes in their gut microbiome, and Sisodia and colleagues have previously reported that gut bacteria may influencethe development of these symptoms in rodents. Long-term antibiotic treatment limited the formation of amyloid plaques and reduced microglia activation in male, but not female, mice expressing mutant proteins associated with familial Alzheimer’s disease. “While compelling, our published studies on the role of the gut microbiome on amyloid plaque formation were limited to a single strain of mice,” Sisodia says.
In the new study, Sisodia and colleagues therefore examined the effects of antibiotics on a different mouse model of Alzheimer’s disease known as APPS1-21. Long-term treatment with a cocktail of antibiotics again reduced the formation of amyloid plaques in male mice but had no effect on females. Antibiotic treatment also appeared to alter the activation of microglia in male mice, changing them from a form that is thought to promote neurodegeneration to a form that helps to maintain a healthy brain.
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