The Gut-Brain Axis

-Ellie Swan

Imagine yourself standing alone in a room. Even when there are no other people or animals around, we are constantly surrounded by tiny beings. These beings are microorganisms such as bacteria. Now, most of us are used to the notion of ‘Germs are bad’. We are taught from a young age to protect ourselves using barriers such as our skin or latex gloves, and practicing daily habits such as washing hands, taking showers or disinfecting surfaces. Ultimately, however, any attempt to keep bacteria away from us is futile. Despite our best efforts to keep them out, many microbes are actually inside of us.

The average human is comprised of approximately 37.2 trillion cells. In addition to this, there are around 39 trillion bacterial cells residing within each of us. A majority of these microbes live in our gut, or intestines. Contrary to our preconceptions, we actually rely on the microbes to perform many bodily functions. Surprisingly, the symbiotic relationship between gut bacteria and the human body has been around for as long as our species has existed and is essential for our survival.

Over millenia, the gut microbiome and the human brain have evolved to not only coexist, but to communicate with one another. The hypothesis that our gut and brain are linked was first notably discovered in the 1820s when the army physician William Beaumont was presented with a patient who had been hit by a bullet to the abdomen. The hole created by the bullet never healed properly, leaving the now infamous patient in a unique state. Dr. Beaumont used this unusual wound to broaden his knowledge on human digestion, whereby he discovered a link between digestion of food and the patient’s emotional state. In recent years, there has been increasing study on the connection between our intestines and our brain, a concept which we now call the gut-brain axis. As of current knowledge of human physiology, the bacteria which colonize our gut communicate with our brain and vice versa. In this way, microbiota have been shown to influence and be influenced by our mental health and emotions.

So how do the brain and gut communicate?

In terms of communication pathways, one key component is the enteric nervous system (ENS). This part of the peripheral nervous system is comprised of the nerve cells lining your GI tract and mainly relays information involved in controlling digestion. A particularly new and interesting field of research around the ENS are the so-called neuropods. Neuropods are processes belonging to enteroendocrine cells, a cell type which lines the inner wall of the small intestine, facing the intestinal lumen. In response to information sensed from bacteria or food passing them in the gut, the enteroendocrine cells relay signals along the neuropods which synapse (connect with) afferent nerve fibers, thus carrying the information directly to the brain. The connection between these cells and the brain is formed by the Vagus nerve. The Vagus nerve, 10^th of the cranial nerves, sends signals bi-directionally (two and from the brain) as it contains both afferent and efferent fibers.

If the Vagus nerve is the highway, then neurotransmitters are the cars travelling along it. Commonly, we assume that neurotransmitters are primarily concerned with the brain and thus produced and active there. While this is largely correct, some neurotransmitters are actually produced in the gut. For example, serotonin, which contributes to feelings of happiness and GABA, which reigns in feelings of fear or anxiety are among those chemicals which are produced in the intestines in addition to the brain. Apart from neurotransmitters, the gut also produces short-chain fatty acids which affect the brain in a number of ways, for example by influencing appetite, as well as some substances with immune functions, involved in inflammatory response. Collectively, substances produced or present in both the brain and gut can travel via nerve pathways or the blood stream to exert a specific effect on their target organs.

Since imbalances in gut microbiota are linked to disease, you could ask what the ideal ratio of bacteria for optimal health is. Unfortunately for us, there is no answer to this question. Regardless of health status, the structure of the microbiome varies between individuals.

Shaped early in life by birth delivery mode, breast feeding, use of antibiotics and throughout our life by our lifestyles, our microbiomes are unique in many ways. Before birth, our intestines are largely sterile, void of any bacterial content. At delivery, our bodies are populated mainly by our mothers’ vaginal bacteria. Babies born by c-section lack this dousing in essential bacteria, thus the effects of this are a hot topic in current gastrointestinal research labs. Throughout life, the structure of the microbiome changes in response to environmental factors, while a ratio of certain phyla should (and usually does) stay constant to maintain bodily health. The dominant phyla in the gut throughout human life are firmicutes and bacteroidetes. The ratio between these two phyla is used as a biomarker for gut health. A more diverse microbiome is associated with good health in general, while exercise has been shown to increase microbial diversity along with other factors.

One field in which many scientists have explored the connection between brain and gut is stress research. Since it is actually your microbiome that regulates processes in the brain, scientists have been led to believe that neurological malfunctions may be ameliorated by targeting the bacteria in our intestines.  Confirming this hypothesis, mouse studies have shown that the structure of gut microbiota changes in response to stress, entering a state termed ‘stress-induced dysbiosis’. While stress alters the microbiome, altering the population of bacteria in our bodies has been shown to alter the expression of proteins in the brain, which ultimately influences stress response. When comparing germ-free mice (those that were bred to contain no bacteria and kept in sterile environments) to regular mice, an increased stress response was found in the germ-free variety. Despite only being exposed to light stressors, the sterile mice produced excess amounts of stress hormones, proinflammatory cytokines and exhibited an increased permeability of the blood brain barrier as well as decreased levels of serotonin (the happiness hormone). As part of experiments with therapeutic approaches to stress, chronic administration of a type of lactobacillus bacteria revealed marked reductions in anxiety-like and depressive behaviors. As a result, we are able to confirm that stress and gut bacteria function as part of a two-way path: Stress exposure influences an organism’s microbiota composition and at the same time, microbial populations can shape the way an organism responds to stress.

Germ-free mice were used not only for stress research, but have also successfully led medical research in the direction of potential therapeutic application of our knowledge about the gut-brain axis. In these studies, the lack of gut colonization caused social behavior deficits in the mice. Germ-free mice are not able to interact with there cage-mates in the same way regular mice do. This is attributed to a decrease in the synthesis and metabolism of neurotransmitter precursors and short chain fatty acids which apparently usually exert important effects on the brain. Lacking the microbiota that produce these neurotransmitters, the mice cannot function properly in a social setting. As part of the experiment, researchers extracted microbiota from healthy (regular) mice and transplanted them into the germ-free mice. The behavioral deficits from before were vastly improved, thus opening the door for bacterial transplant therapies in the future of medical practice.

Apparently, the common notion bacteria having solely detrimental effects on human health and well-being is unfounded. Most bacteria in our bodies actually perform vital function especially in terms of brain development and neurological processes throughout life. Future research into the depths of our GI tracts may allow scientists to come up with new ideas about how to treat diseases such as Alzheimer’s, depression and chronic stress, giving us hope in an ever growing field of medical conundrums.