It is quite likely that you know someone – a close friend, a relative, or even yourself – who suffers from anxiety. With increasing stress and demands from social media, work, and day-to-day life, the incidence of anxiety has increased, and generalized anxiety disorder can affect up to a third of individuals over their lifespan. Many individuals rely on medication which may not fully eradicate symptoms, may have negative side effects, or may not help at all. However, recent research suggests that one answer to improving anxiety management may lie in an unlikely place: maintaining a healthy balance of gut bacteria.

Most of us have grown up with the understanding that “germs are bad” or “bacteria make you sick”. Attitudes such as these are commonplace, and yet they may not be the most appropriate. Despite our best efforts to remainĚýclean, bacteria are present everywhere we go – our homes, public transit, and even on every surface of our bodies. In fact, studies have demonstrated that 99% of the genes in our body actually come from various species of bacteria that reside on our skin and within our digestive tract. Even more surprising, the cells of our body are outnumbered approximately 9 to 1 by bacterial cells! Although many types of bacteria can be responsible for causing illnesses, the sheer number of bacterial cells in our bodies indicates that most bacteria are not disease-causing and some may even be beneficial to our health.

Over the last 15 years, a growing body of research has focused on the diverse ecosystem of bacteria, fungi and viruses residing in our gastrointestinal tract. All together this system is known as the microbiome, and it differs greatly from person to person. The 100 trillion microbes that populate our gut contribute to numerous functions that support our overall health including regulating immunity, absorbing nutrients, and vitamin production, as well as playing a role in our mental health. Interestingly, much like a fingerprint, every individual has their own unique gut microbiome which can be altered by a variety of factors.

So where does this gut microbiome come from? When we are born, our gastrointestinal tract is germ-free because the womb is sterile. Our first microbes come from the birth canal during normal birth, and following this, the general environment. Nutrients in breast milk such as fatty acids and complex sugars feed the bacteria that have colonized our gastrointestinal tract. During early childhood, the food we eat, germs we catch, and activities we engage in slowly solidify the bacterial population and diversity in our gut.

Interestingly, researchers have come to understand that this bacterial population can affect our brain and contribute to anxiety. The brain and the gut communicate through something researchers call . Neurotransmitters are chemicals within the brain that send information from one cell to the next. Many gut microbes can directly change the levels of these neurotransmitters, which might allow them to communicate with neurons. In fact, our gut microbes produce 90% of the serotonin (our feel-good neurotransmitter) in our body. Levels of this transmitter are associated with mood disorders, including anxiety. In germ-free mice with sterile intestines, there is significantly less serotonin found in the blood. This could indicate that gut bacteria signal the brain through release of neurotransmitters. Germ-free mice also have higher levels of the stress hormone corticosterone compared to the mice with a normal gut microbiota and, more importantly, when these germ-free mice were given a single bacterium, their dysfunctional stress response returned to normal. To further strengthen this idea, even short disruption of the balance of the gut, known as dysbiosis, has been linked to lower serotonin levels and anxiety like-symptoms in mice.

Other mouse studies show how the gut microbiota may influence our brain to produce anxious personality types. When germ-free animals were given bacteria from either normal or anxious mice, they took on behaviours from the donor mice, becoming either timid and fearful (markers of anxiety) or more exploratory. Looking to the human condition, we see that anxiety is a common symptom of individuals with irritable bowel syndrome (IBS). When gut bacteria from IBS or anxiety patients were given to mice, . While the majority of research is quick to link exercise to better physical and mental health, it turns out exercise may also increase the diversity of the gut microbiota and alter the levels of some bacteria which have been linked to anxiety.

Although most of these studies have been performed in mice, there is evidence from a growing number of human studies as well.Ěý One particularly interesting study found that . As sociability is normally associated with lower rates of anxiety and depression, the diversity of gut microbes may help predict whether these toddlers will develop anxiety disorders later in life and may in the future be an avenue that could be targeted for treatment.

One cautionary note remains to be discussed: the overuse of antibiotics, consumption of unhealthy foods, lack of sleep, and poor exercise habits can all play a role in reducing the health of our gut. It is possible, although still unknown, that the shift in our lifestyles from manual labour and home-cooked food to relatively static lives and fast food may be playing a role in the increased anxiety we currently face. Thus, simple lifestyle changes and healthy food choices (such as eating fruits, vegetables and fermented foods) to take care of our gut bacteria might be one route to happiness and good mental health.

References:

Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Xiao-Nian, Y., Kubo, C., & Koga, Y. (2004). Postnatal Microbial Colonization Programs the Hypothalamic-Pituitary-Adrenal System for Stress Response in Mice. The Journal of Physiology.

Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K.D., Verdu, E. F., & Collins, S.M. (2011). The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice. Gastroenterology.

De Palma, G., Lynch, M.D., Lu, J., Dang, V.T., Deng, Y., Jury, J., … Bercik, P. (2017). Transplantation of Fecal Microbiota from Patients with Irritable Bowel Syndrome Alters Gut Funtion and Behavior in Recipient Mice. Science Translational Medicine.

Christian, L.M., Galley, J.D., Hade, E.M., Schoppe-Sullivan, S., Kamp Dush, C., & Bailey, M.T. (2015). Gut Microbiome Composition is Associated with Temperament During Early Childhood. Brain, behavior, and immunity.

Monda, V., Vilaano, I., Messina, A., Valenzano, A., Esposito, T., Moscatelli, F., Viggiano, A., Cibelli, G., Chieffi, S., Monda, M., & Messina, G. (2017). Exercise Modifies the Gut Microbiota with Positive Health Effects. Oxidative Medicine and Cellular Longevity.

By Ariel Root

Apply 60 different stressors for half a second each over a one-hour period, and the test animal will appear to be resigned to its fate. Okay. What about applying the same stressor to humans, for 24 hours, every day, for five years? Maybe 80% of those tested might show depressive-like behaviours, but what about the 20% that don’t; what is it about those 20% that make them resilient? How come they can survive greater stressors, and not only survive, but in some cases, flourish? What makes some individuals so resilient, and others so vulnerable?

In the early 1970’s, Hymie Anisman remembers researchers investigating the effects of traumatic events on humans or animals, and asking why they develop feelings of depression. “While that was interesting, it was the wrong question. The question shouldn’t be why [people] fall into a depression, but why didn’t everybody fall into this state?… but of course, that’s very difficult to answer.”

Anisman was a Canada Research Chair in Behavioural Neuroscience, and continues as a Professor in the Department of Neuroscience investigating the influence of stressful events on neurological and immunological changes. He has partnered with researchers internationally, as well as with those from the Royal Ottawa’s Institute of Mental Health Research (IMHR). Using animal models, Anisman and his collaborators are able to introduce a particular social stressor (e.g., a bully, a new environment), observe the resulting behaviours, and link anxiety- or depressive-like behaviors to neurochemical changes in the brain. “Neurotransmitters are signaling molecules, and they can cause other neurons to fire, or stop firing.” This cascade of signals is a complicated process, but Anisman observes these processes, striving to link the release of certain chemical compounds to specific behaviours.

At the beginning of his career, Anisman was involved in the discovery of the multi-hit hypothesis notion, whereby re-exposure to the same, or a similar, stressor can elicit neurological changes at a greater level compared to the first exposure. This discovery was also paired with the suggestion that in many cases, illness development related to depression or addiction is often a result of combination of the stressor, genetics, or early life trauma. This notion of “priming was a big deal, [and one] of the most rewarding findings” for Anisman.

Since then, Anisman has also participated in research regarding the effects of stress on inflammatory processes, particularly as they relate to cytokine activation and distribution. While cytokines are activated under stressful conditions, and intend to be helpful, in high concentrations they can be damaging, and are linked to stroke, diabetes, and depression. “In all cases, inflammation is the common denominator, and can make you more vulnerable” to developing one or more of the other diseases.

Anisman indicates that “brain regions speak to other parts of the brain, but the brain also speaks to other parts of the body… and [I] believe that there is a link between the immune system and the brain.” Through collaboration with researchers at the IMHR, Anisman is researching the effects of various stressors on the gut microbiome following introduction of antibiotics, probiotics, or prebiotics. He is specifically wondering, “if we manipulate the gut, how [could this] affect the immune response, and how could that affect the brain?” The collaborative team is first trying to determine if there is, in fact, a relationship between the gut bacteria and mood states, and if this relationship can be altered through diet or modified gut biome factors.

Anisman has become particularly interested in the human resilience spectrum and to what extent resilience is influenced by psychosocial factors, such as community, religion, or relationships. “Vulnerability and resilience are not two ends of a continuum,” he explains. “If you are very well connected, or have a very good social group, you can cure certain types of conditions. So what are the factors that make a person more or less resilient? What are the genetic factors? The personality factors?” And, while a traditional rodent model can enable observations of hormonal changes in the brain, they are not always ideal for these streams of research, introducing new challenges for Anisman’s research.

Collaborations within ĐÓ°ÉÔ­´´, the IMHR, and with international partners has been rewarding for Anisman. He acknowledges the importance of interdisciplinary teams. “If everybody knew everything, we wouldn’t need teams; interdisciplinary teams allow us to do things we wouldn’t be able to do otherwise.” Venturing into research dealing with the microbiome, Anisman has teamed with other affiliate researchers of the CHAIM centre to enable research regarding psychosocial stressor response and resilience, and early childhood development. “When you have research partners who you can trust, and who know things you don’t, together, with a degree of overlap, you can come up with exciting projects.”

For Dr. Anisman’s contact information, go here.

This is one of the video blogs created by graduate students in the Knowledge Mobilization course in the Health Science Technology & Policy program at ĐÓ°ÉÔ­´´ University.