Antibiotic treatment alleviates Alzheimer’s disease symptoms in male mice, study reveals

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 gut bacteria may influence the 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.

To prove that these improvements in Alzheimer’s symptoms were caused by alterations in the gut microbiome, the researchers transplanted fecal matter from untreated mice into antibiotic-treated animals. This procedure restored the gut microbiome and caused an increase in amyloid plaque formation and microglial activation.

But why do alterations in the gut microbiome only affect male mice? Sisodia and colleagues discovered that long-term antibiotic treatment changed the gut bacteria of male and female mice in different ways. The changes in the microbiome of female mice caused their immune systems to increase production of several proinflammatory factors that could influence the activation of microglia.

“Our study shows that antibiotic-mediated perturbations of the gut microbiome have selective, sex-specific influences on amyloid plaque formation and microglial activity in the brain,” Sisodia says. “We now want to investigate whether these outcomes can be attributed to changes in any particular type of bacteria.”

Story provided by the Journal of Experimental Medicine