The gut microbiome may affect brain aging, mouse studies suggest

The gut microbiome may affect brain aging, mouse studies suggest

By Jackie Flynn Mogensen edited by Claire Cameron

Age changes the brain, but why some people remain mentally sharp well into dotage while others do not is a bit of a mystery. Part of the answer may have to do with genetics, but now a new study in mice suggests it may also have something to do with our gut.

In a series of experiments, researchers found that a communication pathway between the brain and the gut may be integral to how well the brain retains memories.

The genesis of the study came from a chance observation: young, two-month-old lab mice housed with older, 18-month-old mice showed “really impaired cognition,” says Timothy Cox, the study’s lead author and a graduate student at the University of Pennsylvania. He and his colleagues suspected that gut bacteria might be involved.

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In the study, the researchers exposed young mice raised in a sterile, microbe-free environment to gut bacteria from old mice, which caused the younger animals to perform worse on cognitive tests, as if they had aged prematurely, just like the co-housed mice. However, when young mice housed with older mice were given antibiotics, the effect was erased. And older, germ-free mice still had good memory skills. Taken together, the results suggest that bacteria in the guts of the older mice made young mice perform as if they had an old brain.

By sequencing the bacteria found in the feces of older mice, the researchers identified a culprit—a species of bacteria called Parabacteroides goldsteinii.

When the researchers exposed young mice that were raised in a sterile environment or treated with antibiotics to P. goldsteinii, the mice again performed worse in cognitive tests. P. goldsteinii, Cox explains, can trigger inflammation in mice, which can obstruct the vagus nerve – the communication highway that relays signals between the gut and the brain. Stimulation of the vagus nerve also improved the mice’s cognitive performance. The findings were published on Wednesday in the journal Nature.

The findings build on previous research showing that the microbiomes of younger mice can “rejuvenate” the brains of older mice, says John Cryan, professor of anatomy at University College Cork in Ireland, who was not involved in the new study. Several studies over the past decade have shown that the “microbiota-gut-brain axis” can influence brain function. “What this study adds is a much clearer mechanistic pathway,” he says.

Importantly, the study was conducted on mice, and the findings are not readily applicable to humans. The researchers emphasize that the results do not indicate that young people who live with older adults may experience cognitive problems. First, the human gut microbiome is complex in its own way. And for another, mice eat each other’s feces. “I suspect most people don’t,” says Cox.

But the results could one day lead to future therapies for memory problems and cognitive decline in humans. P. goldsteinii is “definitely a member of the human microbiome,” says Christoph Thaiss, an assistant professor of pathology at Stanford University and co-author of the paper. But whether it affects cognitive decline in humans is unclear.

Vagus nerve stimulation, meanwhile, is already an approved procedure for various brain disorders, including stroke and epilepsy.

“It’s definitely not impossible to imagine a future where people stimulate the vagus nerve to counteract cognitive decline,” says Thaiss. “But we would need larger studies and clinical trials to find this out.”

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