Ancient Greek texts describe two opposing rivers running through the underworld.   Their names were Lethe and Mnemosyne. To drink from Lethe caused one to forget. Drinking from Mnemosyne allowed one to remember everything. Millennia later, we’re still fascinated by the same topic. What can we do to improve our memory? Modern science has implicated a wide variety of pathways involved in the memory process. And as research on the subject of the human microbiome expands, we’re increasingly seeing that our resident microbes may be playing a bigger role in this subject than we could have guessed.

Memory is by definition a cognitive process. This means that most of the existing research on the topic relates to our brain health and function. Extreme examples of neurological damage make it clear that our brains are needed to create, store, and recall memories. But while the brain may house the actual machinery, we now understand that influences outside the central nervous system play a major part in every part of the memory process.

As it relates to memory, the idea that what happens in our bodies affects our brains may be best described in Alzheimer’s, the prototypical disease of memory malfunction. Our risk for developing Alzheimer’s has now been strongly linked to our blood sugar levels, our weight, our blood pressure, and even our sleep habits. To further this case, we also know that our immune and endocrine systems influence our brain function and our risk for developing memory issues. And as it turns out, all of these seemingly disparate influences on our brain health interconnect with the microbiome.

In recent years we’ve seen an explosion in scientific publications discussing the microbiome—the collection of all the microbes that live on or in our bodies. Using a variety of investigative techniques, researchers have shown that these bugs, especially those that live in our intestines (the gut microbiome) play a variety of roles in our health. One area of investigation that has drawn a lot of attention is the gut-brain axis.

The idea is simple: our gut (which includes our cells as well as trillions of microbes) is in constant bidirectional communication with our brains. Though it’s easier to conceptualize our brains sending signals to our gut, it’s far more interesting to know that our gut bugs, and more specifically our gut bacteria, are transferring messages up to our brains. Data provided to our central nervous system from the microbiome are thought to influence our neurotransmitters, regulate our neurons, and even shape the structure of the brain itself.

It’s striking to realize that the bacteria in our gut are influencing our brain structure and function. It means that part of what makes us who we are is determined by the microbiome. When more specifically considering how our bugs influence our memory, something else becomes apparent. Our microbiome may play a key role in many of the best-described pathways involved in memory.

It has been recently demonstrated that memory, and more specifically forgetting, may be controlled by the actions of microglia. Animal research over the last decade has shown that microglia prune away weak connections between neurons. This enhances the signal-to-noise ratio for the remaining connections. As stated in a 2020 paper in The New England Journal of Medicine, this breakthrough may open the door to immunity-based memory therapies.

Microglia have also been implicated in other memory-related processes. For example, we know that an area of the brain called the hippocampus is critical for memory consolidation. People with damage to the hippocampus have major issues forming new memories, and damage to the hippocampus is one of the hallmark features of Alzheimer’s disease. Notably, the hippocampus is one of the few regions of the brain thought to grow new neurons across the lifespan. But activated microglia seem to disable this process through the release of inflammatory molecules.

If microglia are in fact key stewards of our memory, we need ask how to preserve their healthy function. To this end, it’s very important to recognize that microglial dysfunction is thought to be a common factor in a variety of brain diseases ranging from depression to Alzheimer’s. This interesting fact seems in part a reflection of a property of microglia: they appear to act as translators of immune messages from the body into the brain. In pathologic conditions like depression and Alzheimer’s disease, microglia create problems in part by sensing and amplifying inflammatory signals from the rest of the body. Moving upstream, if microglia are pathologically activated by systemic inflammation, we have to ask what regulates systemic inflammation. Here again, the gut and the microbiome take center stage.

It’s been established that up to 70% of our immune system resides in and around our gut. These immune cells are in close proximity with the gut microbiome and engage in a continuous exchange of data with these bugs. Indeed, the healthy function of the gut immune system is dependent on the gut microbiome. In addition to directly supporting balanced gut immunity, these gut microbes also take partial responsibility for maintaining the integrity of the gut lining. It is increasingly recognized that a permeable gut barrier (sometimes called leaky gut) may trigger systemic inflammation. So, to help prevent the type of widespread inflammatory immune dysfunction that can reach the brain, activate microglia, and compromise our memory, a healthy microbiome appears essential. 

Over the last 50 years, scientists have gained tremendous insight into the effects of stress on the brain. Chronic elevations in stress hormones like cortisol appear to preferentially affect specific areas within the central nervous system. And of these, the hippocampus is particularly vulnerable. Sustained exposure to stress is associated with atrophy of the hippocampus—a literal shrinking in its size.

Chronic, sustained life stress has been linked to a higher risk for developing dementia. And it’s now understood that the microbiome helps regulate this stress response.