How Anxiety & Depression Can Come From Our Gut
The Gut-Brain Axis and the research around it has long been a topic mired in “researcher speak”, that is to say, lots of complicated terms that mean very little to anyone who doesn’t work in a lab or read scientific literature for fun.
I remember the first time I attended a lecture on the Gut-Brain connection at a research symposium. At the time, I was in my undergraduate degree and considered myself a very science-literate person, but when a University of Toronto researcher got up in front of the crowd and began to talk in depth about the neural, psychological, physiological, immunological, and biochemical connections between the gut and the brain, my jaw fell open, my eyes glassed over, and I spent the next 40 minutes wondering if he even knew what he was talking about because it all sounded like gibberish.
Fast forward 7 years and now as a Naturopathic Doctor I work with the Gut-Brain link all the time in private practice. Over and over again I see poor digestion and digestive health as the root cause of mental health concerns or brain-based diagnoses. That said, I still find it a struggle to explain the connection to my patients - who knew spending an hour with a patient still wasn’t enough time! I’ve had people reach out to me and ask for more resources on the gut-brain connection, to which I refer them to any one of these fantastic books, but I can’t help feeling that in the busy world we live in, there has got to be a better way to translate this information so that we may all learn and benefit.
The Gut-Brain Reading List:
The Mind-Gut Connection
Beyond the Label
When the Body Says No
Brain Maker
The Second Brain GUT
Hence, the reason for this article - the Gut-Brain link explained in Coles Notes fashion! Well let’s just dive right in...
What Is The Gut-Brain Connection?
The Gut-Brain Axis, or GBA for short, refers to the bidirectional communication between the gut and the brain. This is essentially saying the the gut and the brain talk to each other; they can even influence how the other one functions - if one gets sick, it can make the other one sick too, just like if your partner gets the flu and then 3 days later you find yourself in bed with your own barf bucket. Bidirectional communication.
The gut and the brain talk to each other in a couple of different ways. You probably learned way back in high school that our brain is connected to everything in our body; it is our organ of function - through nerves it tells us how to keep breathing, how to keep our intestines undulating so that food will move through, etc. On a deeper level, the brain / nervous system can influence how the gut moves, how much mucus is secreted, and more. This input can greatly impact which microbes make a home in the gut. For example, if the nervous system stops telling the gut to move often and move well (which may happen as a response to stress, medication, endocrine issues like hypothyroidism, etc), microbes that should have been flushed from the small intestine, aren’t flushed, so they take up residence in a part of the gut that they shouldn’t. This is actually the mechanism by which Small Intestinal Bacterial Overgrowth occurs, or SIBO for short. SIBO is thought to be responsible for up to 50% of IBS symptoms; chronic bloating, fatigue, constipation and diarrhea, abdominal pain. Diagnosing and treating SIBO thus involves not only changing the gut flora, but affecting how the brain and nerves talk to the gut. I have watched many a patient who struggled with vague IBS symptoms for years, recover with the diagnosis and treatment of SIBO.
But I digress. I just get really excited about SIBO because it is the missing link so many people have been searching for when it comes to healing.
So we can begin to see how the brain has an effect on the function of the gut - but how does the gut talk back to the brain and influence the development of anxiety, depression, autism and more?
In keeping with the Cole’s Notes directive, let’s take a quick look:
How the Gut Can Influence Brain Function
#1. The little bugs that live inside your intestine have DNA of their own, and essentially, act like little masterminds that can support or hinder mental health and brain health. Here are but a few examples of how these bugs can affect us mentally:
Certain strains of bifidobacterium and lactobacillus make GABA, one of our calming neurotransmitters that is often supplemented or addressed in treating anxiety.1 The gut microbiota are also responsible for a large percentage of our serotonin production. Serotonin you may recall, is the key neurotransmitter that many antidepressant medications target!
Through the vagus nerve, a very long nerve considered part of the parasympathetic nervous system that may be thought of as a major highway between the gut and the brain (imagine the 401 my GTAers), certain probiotic strains have been shown to be able to change the genetic expression of GABA receptors in the brain (GABA receptor function is implicated in anxiety and autism) and decrease cortisol (our stress response hormone that when thrown out of whack, can affect the immune system, weight gain, blood sugar regulation, memory and more!).2
Humans with diverse and healthy gut microbiota (which is referring to the whole lot of little bugs that live in a gastrointestinal tract) were found to make enough butyrate, a short chain fatty acid that specifically improves the regulation of the immune system to shift the body away from a state of allergies and autoimmunity.3,4 Keep this in mind as we will soon talk about how the gut can affect the immune system which can in turn affect the brain, leading to anxiety, depression and other neuropsychiatric diagnoses like autism.
Bifidobacterium, a species of bacteria in the gut, has been shown to increase levels of something called Brain Derived Neurotrophic Factor (BDNF). BDNF, while sounding super complicated, actually helps us build neurons in the part of brain that regulates our emotions and our cognition, two key parts of our mental health.5 This was studied in mice that were considered “germ free” (no gut microbiota), and once these mice were colonized with a healthy bifidobacterium, their BDNF levels increased and this changed their brain function!2 How insanely cool is that?!
The overgrowth of bacteria (as in Small Intestinal Bacterial Overgrowth [SIBO]) can block the absorption of key nutrients like iron, proteins, Vitamin B12, fat soluble vitamins, and actually increase circulating levels of folic acid in the blood. This, along with some toxic products made by imbalanced gut bacteria, impairs the methylation cycle, an essential biochemical pathway by which the body transfers methyl groups between molecules to accomplish DNA repair, gene regulation, detoxification pathways and more. Poor methylation (either over or under methylation) is implicated in many chronic conditions and is a key piece in treating unique cases of chronic anxiety, depression and autism.
The gut is home to not only bacteria, but also to some viruses and yeast species. Multiple studies have investigated the role of certain strains of Candida in the influence of Autism Spectrum Disorder in children. Research is now looking into how yeast species can change the minerals we absorb and how certain yeast can produce compounds like propionic acid and ammonia that may form betaalanine and increase autism symptoms.6,7
#2. Inflammation within the gut itself can lead to intestinal permeability, or the better known phenomenon of leaky gut syndrome.
—> What Is Leaky Gut Syndrome? When our gut flora is not healthy (or in other words, dysbiotic - the opposite of symbiotic) and the walls of our gut are subject to inflammation, the cells themselves become puffy and inflamed. This causes some separations between the cell junctions and contents of the gut can “leak” into systemic (full body) circulation.
—> What leaks out of the gut in leaky gut syndrome? Food particles, allergens that may have been swallowed, bacteria, yeast, and more.
—> Why is this leaking a problem? This is where the immune system comes in. The gut wall is essentially our barrier between our body’s inner world and that of the outer world - our skin is another good example of a barrier. The gastrointestinal tract tube that runs through our body is very much exposed to the outer world via food & drink and is subject to less control by the immune system. Once food or bacteria leak into the body they become an “antigen”. An antigen is anything that has the ability to create an immune response. Bacteria and food are very good at creating immune responses which are at the root of food sensitivities and the makings of autoimmune disease. When the immune system is triggered by foreign antigens that have leaked inappropriately from the gut, it gets all fired up and begins to make antibodies. In this firestorm of fierce antibody production, particularly if we don’t make enough of the regulator cells that calm the immune system down once it gets going (kind of like anger management & meditation for the immune system), our body can accidentally present “self antigens” to the immune system, and so antibodies begin to be created against our own tissue. Antibodies created to attack and destroy brain and nerve tissue is not an ideal situation. Even without autoimmune presentations, microbes that have leaked into systemic circulation cause an upregulation of inflammatory immune molecules, called cytokines. Some of these cytokines can increase the permeability of another barrier, called the Blood-Brain Barrier, otherwise known as the BBB. The BBB acts as a bodyguard between the environment around the brain and that of the rest of the body, only selectively allowing certain substances to pass into the brain space (VIP pass required!). Once this barrier has been compromised, inflammatory molecules and other rogue proteins that shouldn’t have been invited to the brain party, can cross the BBB and cause inflammation in the brain itself. This is thought to be at the root of many anxiety, depression and dementia cases.8,9,10
#3. The gut microbiota can affect our hormone function, and hormones like Estrogen, Progesterone, Cortisol, Insulin, Testosterone, Melatonin and more have a big affect on our mental health. This could be a whole new article on its own. Check out this other article on Estrogen Dominance and High Functioning Anxiety for a bit more information.
Wrap Up; How Can Depression & Anxiety Really Manifest From Poor Gut Health?
Coles notes of the Coles notes. Because I really could go on forever, and in the end, the in- depth scientific data just serves to tell us what Naturopathic Doctors already know: a body and mind need to heal together. We cannot compartmentalize parts of the body and expect each compartment’s dysfunction to not impact the other compartments. This mechanistic, reductionist way of thinking may be helpful in surgery, but not when it comes to healing chronic conditions.
Snapshot Recap:
The gut bacteria themselves create neurotransmitters and make compounds that affect mental health & cognitive function. The gut microbiota can affect circulating hormones and receptors in the brain through the vagus nerve highway.
Inflammation in the gut leads to inflammation of the brain via the immune system. Inflammation in the brain hurts our emotional and cognitive health.
Any breakdown in our brain and nerve functioning, from trauma, medication, hormone dysregulation, other causes of mental health concerns, etc, can change the way our gut moves and functions which changes the composition of the gut microbiota.
Our diet, stress levels and lifestyle dramatically affect what lives in our microbiome. Our gut microbiota affect what nutrients we absorb and utilize from our diet.
How Does The Gut-Brain Link Affect The Way I Handle My Anxiety & Depression Symptoms?
Knowing more about the gut-brain (and immune) connection reinforces one key aspect that I believe we must always come back to when we want to heal: The body works as an interconnected organism; to heal one part of it is to heal all of it, and to heal our body as a whole usually means we need to heal the the way we eat, think and live.
When I work with patients on their gut brain axis, we always begin with the basics: Diet, Perception of Stress and Sleep Quality. Then we look deeper at imbalances that the body needs some support correcting: Is there dysbiosis in the gut that is at the root of metabolic issues? How is the thyroid functioning? Is there a picture of endometriosis? Has there been a n exposure to toxic elements like mold or high amounts of heavy metals? Are the methylation and detoxification pathways functioning well? As the body heals we want to look at how imbalance began in the first place, and always seek to address this to prevent recurrence of an unhealthy gut. This is holistic, integrated medicine and I believe it serves the gut-brain connection very well.
As Hippocrates is credited with saying after a lifetime of work in medicine and the human body: “All disease begins in the Gut.”
References:
1. Wright ML, Starkweather AR. Antenatal microbiome: potential contributor to fetal programming and establishment of the microbiome in offspring. Nurs Res 2015;64:306-19. [PubMed]
2. Cryan JF, Dinan TG. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 2012;13:701-12. [PubMed]
3. Islami F, Ren J-S, Taylor PR, Kamangar F. Pickled vegetables and the risk of oesophageal cancer: a meta-analysis. Br J Cancer 2009;101:1641-7. [PMC free article] [PubMed]
4. Schroeder FA, Lin CL, Crusio WE, Akbarian S. Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiat 2007;62:55-64. [PubMed]
5. Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota’s effect on mental health: The gut-brain axis. Clin Pract 2017;7(4):987.
6. Burrus CJ. A biochemical rationale for the interaction between gastrointestinal yeast and autism. Med Hypotheses 2012;79:784-5. [PubMed]
7. Kantarcioglu AS, Kiraz N, Aydin A. Microbiota-gut-brain axis: Yeast species isolated from stool samples of children with suspected or diagnosed autism spectrum disorders and in vitro susceptibility against nystatin and fluconazole. Mycopathologia 2016;181:1-7. [PubMed]
8. Gądek-Michalska A, Tadeusz J, Rachwalska P, Bugajski J. Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep 2013;65:1655-62. [PubMed]
9. Ohland CL, Kish L, Bell H, et al. Effects of lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinol 2013;38:1738-47. [PubMed]
10. Muscatello MRA. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome. World J Gastroenterol 2014;20:7570. [PMC free article] [PubMed]
Dr. Nicole Roberts
is a Naturopathic Doctor practicing in Toronto ON who has a clinical focus on mental health concerns, dementia concussion recovery and ADHD. Her goal is to build an institute dedicated to the research & treatment of Brain and Immune Health while working with Medical Doctors and other medical specialists to advance the health of our children. Dr. Roberts continues to be an advocate for community health as basis of individual health.