New Delhi, March 12 Remotely changing the composition of the gut microbiome by stimulating the vagus nerve, which sends signals from the gut to the brain, may help reverse age-related memory loss, according to a new study.
Studies are looking at the gut as a solution to health issues arising due to aging.
"We wanted to understand why some very old people remain cognitively sharp while others experience significant declines starting in their 50s or 60s," said Christoph Thaiss, a senior author and assistant professor of pathology at Stanford University.
"We learned that the timeline of memory decline is not fixed; it is actively regulated in the body, and the gastrointestinal tract is a crucial regulator of this process," Thaiss said.
The study in mice, published in the journal Nature, showed that the composition of the naturally occurring bacterial population living in the gut, known as the gut microbiome, changes with age – favoring certain types of bacteria over others.
Changes in the gut microbiome are registered by immune cells in the gastrointestinal tract, which trigger an inflammatory response that hinders the ability of the vagus nerve to signal to the hippocampus – a brain region that helps form memory and navigation, the researchers said.
Stimulating the activity of the vagus nerve in older animals was seen to turn old, forgetful mice into "sharp" mice who were able to remember new objects and escape from mazes as easily as their younger counterparts.
"Our study emphasizes that processes in the brain can be modulated through peripheral intervention. Since the gastrointestinal tract is easily accessible orally, modulating the abundance of gut microbiome metabolites is a very appealing strategy to control brain function," said Maayan Levy, a senior author and assistant professor of pathology at Stanford University.
The researchers housed young (two-month-old) mice together with old (18-month-old) mice. Living in close proximity exposed the young mice to the gut microbiomes of the old ones and vice versa. After one month, the compositions of the microbiomes of the animals were examined.
Specific changes in the gut microbiome composition of ageing mice included an increase in the abundance of a bacteria called Parabacteroides goldsteinii, which is directly associated with cognitive decline in the animals.
The researchers showed that colonizing the guts of young mice with the bacteria inhibited performance on object recognition and maze escape tasks, with the cognitive deficit correlated with reduced activity in the hippocampus.
However, treating old mice with a molecule that activates the vagus nerve revealed that the cognitive performance of the animals was indistinguishable from that of young animals.
Further experiments showed that an increasing prevalence of the Parabacteroides goldsteinii bacteria correlated with an increasing amount of metabolites called medium-chain fatty acids, and that these metabolites cause a group of immune cells in the gut called myeloid cells to initiate an inflammatory response.
The researchers said that the inflammation inhibits the activity of the vagus nerve, the hippocampus, and the ability to form lasting memories.