Age changes the brain, but why some people remain mentally sharp well into their dotage while others don’t 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 could 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 holds on to memories.
The genesis for 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 gut bacteria might be involved.
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In the study, researchers exposed young mice raised in a sterile, microbe-free environment to gut bacteria from old mice, causing the younger animals to perform worse on cognitive tests, as if they had prematurely aged, just like the cohoused mice. When young mice that were housed with older mice were given antibiotics, however, the effect was erased. And older, microbe-free mice still had good memory skills. Taken together, the results suggest that bacteria in the older mice’s gut made young mice perform like they had an old brain.
By sequencing the bacteria found in older mice’s feces, 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 could hinder the vagus nerve—the communication highway that conveys signals between the gut and the brain. Stimulating 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 brain in older mice, says John Cryan, a professor of anatomy at University College Cork in Ireland, who was not involved in the new study. Multiple 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 in mice, and its findings are not easily applicable to humans. The researchers emphasize that the results don’t indicate that young people who live with older adult humans might experience cognitive issues. For one, the human gut microbiome is complex in its own way. And for another, mice eat each one another’s feces. “I suspect that most people are not doing that,” Cox says.
But the results could one day lead to future therapies for memory issues and cognitive decline in people. P. goldsteinii is “certainly a member of the human microbiome,” says Christoph Thaiss, an assistant professor of pathology at Stanford University and co-senior author of the paper. But whether it affects cognitive decline in humans is unclear.
Vagus nerve stimulation, meanwhile, is an already approved procedure for various brain conditions, including stroke and epilepsy.
“It’s definitely not impossible to imagine a future where people stimulate their vagus nerve to counteract cognitive decline,” Thaiss says. “But we would need larger studies and clinical trials in order to figure this out.”