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Microbes in your gut might be impairing your memory

Gut microbes send different signals to the brain in people with obesity

Simon Spichak

Neuroscience

University College, Cork

Sometimes when I am in a hurry in the morning, I have trouble finding my keys. After searching for 15 minutes, I usually make my way downstairs for some breakfast. After I take a few bites, I remember that they’re still in the pocket of my coat. It turns out what you eat — and the brainless microorganisms that break down your food — can impact your memory!

Food is a well-known contributor to our overall health, feeding both our bodies and our minds. Eating feeds the trillions of microbes living within our guts. These microbes are not passive inhabitants; they also help us digest our food, turning it into chemical signals that affect our nervous systems.

A recent study published in Cell Metabolism found by-products of gut microbe digestion affected cognitive function and memory of people with obesity. Detecting these by-products early could be critical to modifying our diets to prevent memory impairment.

The authors recruited 65 middle-aged people with obesity and 51 middle-aged people without obesity for their study. Each participant provided fecal samples, supplying researchers with a snapshot of the microbes living within their guts. 

Each participant also underwent a test of short and immediate term memory called the California Verbal Learning Test-II. As part of the test, each person receives a list of words; 30 minutes later, they were asked to recall which words appeared on this list.To challenge their memories, participants were also shown a decoy list. These words were meant to interfere with their memories of the original words. To figure out whether there was a difference in short-term memory between the participants with obesity and those without, researchers asked the participants to remember a long number digit-by-digit. Imagine being shown a credit card number very briefly, and then being asked to recite it backwards just a moment later. Finally, to understand if specific bacteria were associated with brain structure and connectivity, each participant had their brain imaged. The types of bacteria found to influence memory were then fed to mice. This technique, called fecal matter transplantation, tests whether introducing specific bacteria into mice will change their behavior.

Working memory is used in a variety of cognitive tasks, including reading.

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Researchers first noticed that people with obesity performed worse on the California Verbal Learning Test. After controlling for age, sex, depression scores and other factors, they then attempted to associate the abundance of specific microbes found in participants’ fecal samples to their neuropsychological scores. Indeed, the amounts of a few types of microbial species in a person's fecal sample correlated to their performances. Memory scores were positively associated with the abundance of bacterial species in the Clostridium, Ruminococcus, and Eubacterium genera. All of these bacteria help us break down dietary proteins and fibres. The by-products that they leave behind can then travel through our bloodstreams and communicate with distant areas of our body. Some bacteria are even associated with the size of the left hippocampus, a seahorse-shaped region of the brain that plays an important role in verbal memory

Since the researchers didn’t know why they saw this connection, they decided to look at the microbial by-products. Using a technique called metabolomics, they identified what is essentially microbial waste in the participants’ blood and poop samples. They found microbial-by products associated with performance on the memory tests. One such by-product was tryptophan, a by-product of breaking down dietary protein (like Thanksgiving turkey), which was elevated in the poop of people with obesity. Since a lot of tryptophan ended up in their poop, the scientists reasoned that it wasn’t being absorbed into the bloodstream. Tryptophan is also required for making the neurotransmitter serotonin that impacts our mood, as well as other signals shown to affect memory in rodents. Could this explain the connection between gut microbes and memory? 

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The researchers turned to mice to help them answer this question. In general, when scientists try to figure out whether microbes influence behavior, they feed mice poop containing the microbes in question. Mice already eat poop naturally so they’re more than happy to help.

A third of the mice in the study were fed feces from people without obesity who scored high on the memory tests. Another third of the mice ate feces from participants without obesity who performed poorly. A final group received a saline solution rather than feces, acting as a control. The researchers found the microbes associated with worse memory in humans, also impaired memory in mice.

Despite using so many different techniques to confirm their findings, the researchers still acknowledged limitations within their study. It is often hard to conduct large human studies because of the cost, effort and time required to perform them. As a result, this study could not look at different types of metabolic syndrome or obesity. Hormones and brain circuits in the body can go awry for many reasons, so we shouldn't expect one single explanation to apply to everyone. It's also important to note that obesity in and of itself is not an indicator of good or bad health, and the results seen here could arise from complex interactions beyond the scope of the study.

Understanding how specific food and microbial signals might impair our memory would allow for personalized health interventions. Eating right could keep your brain age healthily. It could actually help you find your keys sooner, too.