A GUT FEELING
DID YOU KNOW THAT OUR BODIES HAVE MORE BACTERIAL GENES THAN HUMAN GENES?
Did you know that our bodies are mostly bacteria? For every human cell in our body, there are ten tiny microbes living on our skin, in our mouth, or throughout our digestive tract. Humans and bacteria have evolved together for thousands of years. We have a symbiotic relationship with our bacteria: they rely on us for a safe environment and a regular food supply, and in turn, they help us digest our food and produce chemicals that increase our evolutionary fitness as a species. The bacterial population in our gut alone weighs 2-3 pounds, which is about the same weight as the brain! In fact, our gut bacteria may actually have a bigger effect on our brains than we realize.
Several recent studies have linked gut bacteria with behavior. Mice are one of the best animal models for studying bacteria in the gut (aka the “gut microbiome”) because it is possible to raise germ-free mice – that is, mice that don’t have any gut bacteria at all. In the womb, mice – and humans – are free of microbes. To keep mice germ-free, researchers remove the baby mice by cesarean section and raise them in a sterile environment, so they are never exposed to microbes. Although germ-free mice are not especially relevant to any human condition, they serve as an important experimental control: researchers can compare normal mice to germ-free mice, to determine whether or not the effects of experimental treatments are due to the presence of gut bacteria.
In 2011, Canadian scientists conducted a study on two types of mice: B mice, which are naturally bold, and S mice, which are naturally shy[1]. First, they fed the S mice antibiotics, killing most of the bacteria in the gut, and found that the mice became more exploratory and less apprehensive as their gut bacteria composition changed. After stopping antibiotic treatment and allowing the gut bacteria to recover, these mice went back to their shy behavior. However, the same antibiotic treatment in germ-free S mice had no effect on their behavior, demonstrating that the behavioral change was not due to the antibiotic treatment per se, but due to the change in gut bacteria. Additionally, these scientists colonized the guts of germ-free S and B mice with bacteria from the opposite type of mouse (the S mice got the B mouse microbes, and the B mice got the S mouse microbes). They found that the S mice became more bold, and the B mice became more shy.
Clearly, the gut microbiome can have a major effect on mouse behavior. But can the presence or absence of certain gut bacteria also affect human behavior? This question is more difficult to answer because we can’t use the same techniques on humans that we use on mice: we don’t have germ-free humans. In addition, excessive use of antibiotics to deplete bacteria in the human gut is discouraged because of concerns of side effects and antibiotic resistance. Instead, the role of the human gut microbiome can be tested using probiotics: foods or supplements that contain living bacteria that are known to be safe or even beneficial for our guts.
In a recent study, 60 healthy people took a series of surveys to quantify their psychological health, including levels of anxiety, depression, and perceived stress. Then half of the study participants were given probiotic milk to drink every day for a month while the other half was given a placebo drink. After the month was up, everyone re-took the same surveys. Interestingly, participants who had the probiotic drink showed lower psychological distress, depression, and anxiety, whereas the placebo-drinking participants remained the same. There were physiological differences as well - the probiotic-drinking participants had lower levels of the stress hormone cortisol in their urine.
So what’s going on here? How can gut bacteria affect behavior, anxiety, depression, and stress? This question is a hot new topic of research, and has not yet been fully answered. However, we do know that the biochemical connection between the gut and the brain (also called the “gut-brain axis”) is partially mediated by hormones. Hormones are small signaling molecules that are transported through our bodies by the circulatory system. These molecules then bind to receptors on the surface of cells (including brain cells) to induce a response in those cells, often leading to a behavioral outcome.
There are several hormones that are responsible for regulating our mood: serotonin, which increases our feelings of well-being and happiness; dopamine, which causes the feeling of reward we get from pleasurable experiences; and norepinephrine, which stimulates alertness and contributes to the fight-or-flight response. It turns out that the majority of the serotonin and dopamine in our bodies is produced by cells lining the walls of our small intestine. It is likely that the bacteria in the gut influence production of these hormones (for example, by secreting precursor molecules – molecules that are used to synthesize the hormone) or even produce hormones themselves. In fact, B. subtilis (a bacterial strain commonly found in probiotic yogurt) produces and secretes both dopamine and norepinephrine.
How can we use what we already know about our gut microbiome to help us? Anxiety disorders are the most common mental illness in the US, affecting 18% of adults. Depression (major depressive disorder) is the leading cause of disability. Modifying our gut bacteria using probiotics could be a game-changer in the treatment of these disorders. For example, most anti-depressants work by modifying how the brain responds to a specific hormone such as serotonin, dopamine, or norepinephrine. Instead of changing our brains to combat a hormonal imbalance, imagine using a probiotic supplement to help our gut bacteria regain balanced regulation of all three of these hormones.
Our relationship with our gut bacteria is highly complex, and the studies mentioned here are only the tip of the iceberg. As gut microbiome research grows, new discoveries will change the way we think about our gut bacteria. If you are interested in learning more about your own microbiome, you can have it analyzed through services such as ubiome.com.
These mice are actually called NIH Swiss and BALB/c; names were changed to B and S, respectively, for simplicity.
