Brain aging: Gut microbiome may drive memory loss via vagus nerve - Medical News Today

- A study in mice concludes that age-related loss in memory function may be driven by changes in the gut microbiome.

- This effect is mediated by sensory neurons in the gut that contact the brain via the vagus nerve.

- The scientists identified a mechanism by which gut-brain signals can impair memory formation in the hippocampus.

- Importantly, the researchers also identified ways to reverse the decline in cognitive ability.

On average, human memory declines with age. However, there is substantial variation among individuals: some experience a rapid decline, whereas others barely notice a change.

With our rapidly aging population, understanding why some people are affected while others are not is important work.

A new animal study, published in Nature, concludes that memory problems associated with age may be driven by our gut and the bacteria that live within it.

In particular, the effect appears to depend on how the body perceives and responds to its internal environment, which is called interoception.

Their results may inform novel approaches to mitigating age-related memory deficits. Although the study is in animals, the results are likely to spark much more research.

Interoception and why it matters for memory

Exteroception is our ability to sense the outside world: Sights, smells, sounds, and so on. Interoception, on the other hand, is the body’s ability to monitor its internal state.

The vagus nerve, which travels between the brain and all the major organs, is a superhighway for interoreception. It sends messages from the body to the brain, where it can make any necessary adjustments based on the new information.

Neuronal engrams, or memory traces, are the fundamental unit of memory storage. These clusters of neurons form during learning and store a memory. When we experience a relevant cue, the engram is activated, and we access the memory.

Our ability to form these engrams declines as we age. The researchers hypothesize that communication between the body and brain may be disrupted during aging, which might help explain memory decline.

According to the authors, existing evidence suggests that the gut microbiome “may contribute to age-associated memory loss,” so they started there.

Their research unravelled a relationship among microbes, the chemicals they produce (metabolites), and the immune system, the vagus nerve, and the hippocampus — a part of the brain pivotal for memory formation.

Reading more like a detective novel than a scientific paper, the team slowly unravels this complex web of interactions in minute detail.

Like many systems in the body, the gut microbiome slowly changes with age. The same is true in mice. For the first leg of the experiment, the scientists used various methods to alter a young mouse’s microbiome to more closely resemble that of an older mouse.

They did this, for instance, by using poop transplants or simply by housing a young mouse with an older mouse.

When a young mouse had an old microbiome, it exhibited cognitive decline similar to that observed in an older mouse. If it was then treated with antibiotics, which wiped out the microbiome, their cognitive abilities returned.

This evidence indicates that the microbiome contributes to memory decline with age. Next, they set out to identify which particular bacterial strains might be responsible. They concluded that the most likely candidate was Parabacteroides goldsteinii.

Then, they showed that harbouring an old microbiome, and specifically P. goldsteinii, was associated with altered neuronal responses in the hippocampus. They also noted concurrent changes in other brain regions that process sensory information. This, they theorized, might indicate that cognitive decline is related to disrupted interoception.

Using various techniques, the scientists eventually showed that the vagus nerve was the culprit. Specifically, it was a subtype of neurons called CCKAR+, which pass information from the gut to the hippocampus. These neurons respond to a gut peptide called cholecystokinin (CCK).

When the researchers treated old mice and young mice with old microbiomes with CCK, they recovered their cognitive abilities, becoming indistinguishable from control mice. The same effect was observed when they stimulated the vagus nerve with a GLP-1 receptor agonist, which is another gut peptide.

How do gut bacteria impact the vagus nerve?

This was the next question to answer. Taken together, the researchers had established that increased levels of P. goldsteinii were associated with age-related memory decline and that this decline was due to reduced functioning of vagal neurons that run from the gut to the hippocampus.

This article is republished through the USVI News affiliate desk....