There is an adage that states that we as human beings are what we eat. Studies are demonstrating that this concept has more merit than once believed and when we put into the body those things that not only support physiological needs but also those needs of the commensal organisms that reside within the body all benefit. It is important to understand that these healthy species of microorganisms residing in the GI tract have lived symbiotically with humans since the beginning are responsible for the creation of healthy compounds produced as a byproduct of their metabolism. When patients can recolonize these beneficial microbes their health conditions improve dramatically. Elson M. Haas, MD., the author of several nutrition books to include, The Detox Diet, claims that "gastrointestinal function and ecology are at the core of human health" (Haas & Chase, 2004, p. 13).
The human body hosts about 100 trillion microbes that are very diverse and perform a range of essential and beneficial functions. Our appreciation of the importance of the symbiotic relationship human beings have with these microbial communities to many aspects of human physiology has grown dramatically in recent years (Rogers et al., 2016). This microbiome coexists with gut pathogens, helps regulate the immune system, regulates the endocrine system, and modulates digestion. Eubiosis is state of sufficient friendly flora or bacteria inside the intestines.
When the large intestine is healthy and functioning optimally, it produces friendly flora within the intestinal walls and then releases these microbes into the canal of the intestines as needed. The purpose of this intestinal flora is to manage, guard and protect against the overgrowth of yeast, bacteria, viruses and other germs and worms. Acidophilus and Bifidobacterium are two examples of friendly flora produced by the large intestines.
Dysbiosis, on the other hand, is the opposite of Eubiosis where the intestinal wall has been damaged and is not able to produce these friendly organisms. The most common substances that destroy this ability to produce friendly flora are drugs and in particular, antibiotics (Smith, 1998, p. 13). It is often easy for many to overlook the complexities of modern day living and the factors to take into consideration to support the concept that the condition of this microbiome will often correlate directly with many different aspects of health, not just physically, but emotionally as well.
Many scientists and researchers have come to the knowledge and understanding that the gut is the body's second brain. Today, there is strong evidence from various animal studies done supporting this concept, and that gut microorganisms can activate the vagus nerve. This activation has a critical role in mediating the effects on the brain and in particular, mood and behavior. The vagus nerve is part of the parasympathetic nervous system and is by far very important since it has the most far-reaching effects as it reaches the brain, intestines, stomach, heart, liver, pancreas, gallbladder, kidney, ureter, spleen, lungs, female fertility organs, neck, ears, and tongue (Cohen, 2017).
The vagus nerve seems to be able to differentiate between good and bad microbes where vagal pathways can mediate signals that can both induce anxiety or reduce anxiety depending on the stimulus. When it is experiencing low tone, or lacking in functionality, it can wreak havoc on health in many ways. Poor vagal nerve tone causes digestive disorders, mental and emotional disorders, an increase in the amount of inflammation the body has as a whole, impairs the immune system, and can even cause high blood pressure (Klemer, 2016).
Dysbacteriosis, or another term used to describe gut dysbiosis, the microbial imbalance or maladaptation inside the GI tract and is more commonly referred by health practitioners as "leaky gut syndrome." Specifically, the wall of the intestines is very permeable to tiny particles, usually important nutrients, to allow these to be absorbed and utilized by the body as fuel. Indeed, the primary function of the cells that line the intestines is to regulate this permeability. When things go awry, the cells in the gut can release a protein called zonulin that can break apart the tight fit in the intestinal lining allowing larger particles to go through into the bloodstream that usually results in a heightened response from the immune system and sees these things as foreign invaders to be attacked. Thus, health practitioners will usually see antibodies or specific blood proteins produced in response to and counteracting a specific antigen or foreign invader. Antibodies combine chemically with substances that the body recognizes as alien, such as bacteria, viruses, and foreign substances in the blood (Meyers, 2017). Infections and inflammation, toxins, stress, and age can cause this problem as well. Symptoms of this condition include:
- Gas, bloating, diarrhea or IBS (irritable bowel syndrome).
- Allergies and asthma.
- Hormonal issues like PMS and PCOS (pre-menstrual syndrome and polycystic ovary syndrome).
- An autoimmune disease such as Hashimoto's thyroiditis, rheumatoid arthritis, lupus, psoriasis, or celiac disease.
- Chronic fatigue or fibromyalgia.
- Mood and mental disorders such as depression, anxiety, ADD, or ADHD.
- Skin conditions like acne, rosacea, or eczema.
- Candida overgrowth.
- Food allergies and intolerances (Meyers, 2017).
The goal of the research for this paper is to determine the extent to which gut dysbiosis causes vagal nerve tone imbalance that directly impacts mood and mental health. Conventional medicine often approaches mental health issues with a treatment paradigm meaning that they go after to neutralize active symptoms in an effort to bring a patient to a neutral point where there is no active discernable symptoms or signs of illness or disease.
On the other hand, practitioners or advocates of alternative or functional medicine believe that there is much more to health than the mere absence of disease or illness. The belief is that optimal health can be achieved by seeking to get at the cause of a health issue, correct it, build the body back to a healthy state. Then by continuing to improve health and wellness, the focus needs to be on a whole person approach that delves into the physical, emotional and mental, as well as the spiritual aspects of the individual. Therefore, when proper communication is disrupted between the gut and the brain due to poor vagal nerve tone and dysbiosis in the GI tract, mental illnesses can often manifest that conventional doctors will ignore because it is their goal to treat the symptoms and not necessarily consider any underlying gut maladaptation or dysfunction.
For this study, various research was collected and synthesized from peer-reviewed works from PubMed online and scientific journals like Trends in Neurosciences from the Department of Psychiatry and Behavioral Neurosciences at McMaster University in Ontario, Canada. Also collected and reviewed were several articles on the topic of gut health in conjunction with comorbid psychiatric disorders written by various health professionals that specialize in this area of expertise addressing the gut-brain axis. The discovery of these articles and peer-reviewed studies was conducted utilizing search engines like Google, Google Scholar, and the PubMed search engine for the MEDLINE database of the United States National Library of Medicine (NLM) at the National Institutes of Health who maintains this database.
Much of the studies conducted to assess how changes in the microbiome affected behavior were done utilizing germ-free (GF) mice and comparing them with conventional house-specific pathogen-free mice with a gut microbiome typical of their species. Various scenarios were developed tested and assessed to try to prove that it was the changes between the microorganisms in the gut and the communication resulting from the vagus nerve. For example, researchers would add specific pathogens to see what changes occurred in the gut environment of these mice then observe and record the resulting changes in behavior. Testing was also conducted with antibiotics, various strains of probiotics and prebiotics, as well as various psychiatric drugs to note any changes in gut microbiota and any corresponding changes in behavior. Studies were also conducted with animals that had their vagus nerve severed to demonstrate the consequences this action would have with these animal's reactions to fearful situations and to prove that the gut can be read by the brain through the vagus nerve.
As far as human studies, there is evidence that probiotic use with human subjects matched the data collected with the same testing done with mice. One example was a double-blind, placebo-controlled, randomized, parallel group clinical trial conducted where healthy subjects were given a mixture of probiotics containing Lactobacillus helveticus and B. longum or placebo for 30 days then evaluated. Questionnaires were used to ask participants to evaluate any changes in their coping mechanisms and feelings of stress to assess levels of anxiety and depression. In other studies, participants were given a probiotic milk drink over a three-week period then assessed for mood and cognition to compare the ratings given before the trial to compare and contrast to the score given afterward. While in another study, patients diagnosed with Chronic Fatigue Syndrome received a certain strain of probiotic daily for two months then evaluated.
Overall, the findings from the various research studies conducted show that the presence of commensal gut microorganisms is critical to many human physiological factors such as immune function, nutrient processing, and in the function of the central nervous system. The most prominent microorganisms that contribute to health and disease are Firmicutes and Bacteroides and to a lesser extent Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia (Foster & Neufeld, 2013). Genetics, metabolism, diet, age, geography or environmental conditions, antibiotic treatments and stress all influence the communication between the gut and the brain as well as individual differences in the risk of illness, disease, and treatment responses. By activating the vagus nerve, we can greatly influence inflammation and the immune system.
Comment: One way to stimulate the vagus nerve and thereby reduce inflammation is through specific breathing exercises as practiced in the Éiriú Eolas meditation program.
The role of the brain influencing body inflammation can be profound. It can influence digestive complaints, high blood pressure, depression or any inflammatory condition. The Vagus nerve reads the gut microbiome which initiates a response to modulate inflammation based on whether or not it detects pathogenic versus non-pathogenic organisms. In this way, the gut microbiome can affect an individual's mood, stress levels, and overall level of inflammation (Klemer, n.d.). Gut microbes represent direct intermediaries of psychopathology, and these research studies examine the mechanisms by which the microbiome contributes to brain development, neurological function, and especially in the case of this study, mental illness.
Specifically, a low vagal tone is associated with depression, chronic fatigue syndrome, cognitive impairment, and much higher rates of other inflammatory conditions. To improve vagal nerve tone, it is important to balance the gut microbiome because the presence of healthy bacteria in the gut creates a positive feedback loop through the vagus nerve thus improving its tone (Klemer, n.d.). In mouse studies when a pup is taken away from its mother, this alters the gut environment which causes things like stress and sleep deprivation which increases cortisol levels in the body. This induces bacterial overgrowth that directly impacts the level of cortisol released by the immune system. Cortisol is the stress hormone that helps a person's fight or flight response to a stressor, however, when present over the long term it can have a progressively destructive impact on health and wellness overall.
In studies with germ-free mice, they were observed to have myelin irregularities in the prefrontal cortex of their brain. Myelin is the part of the protective sheath that covers axons of nerve cells that acts as insulation for the electrical activity in the brain. These types of irregularities have also been demonstrated in people with schizophrenia. When these mice were fed probiotics, this condition was reversed (Hoban et al., 2016). It was interesting to note that just as researchers switched the gut flora between a heavy mouse with those of a germ-free mouse the germ-free mouse became heavy and when a thin mouse's gut flora was shared with a germ-free mouse, that mouse too became thin. When these germ-free mice were given specific bacteria, it affected their behavior, and since gut bacteria produce neurotransmitters such as serotonin and dopamine, altered amounts of these neurotransmitters can be a recipe for violent and aggressive behaviors. Stress hormones feed pathogens, and adrenaline increases biofilm formation which is a living film or matrix formed from the overgrowth of bacteria, fungi, and other microorganisms.
Mice fed a strain of probiotics called Lactobacillus regulated emotional behavior and central GABA receptor expression through the vagus nerve in the study done by (Bravo et al., 2011). GABA is the main central nervous system inhibitory neurotransmitter and is involved in regulating many psychological processes where alterations in GABA expression are implicated in the symptoms anxiety and depression. This study compared normal mice to those who had the vagus nerve surgically cut demonstrating that the vagus can adjust communication pathways between the bacteria exposed to the gut and the brain.
Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutics in stress-related disorders (Bravo et al., 2011). In these test subjects, the brain was still able to send signals down from the brain to the stomach and gut, but unable to send signals from the gut to the brain. Vagus nerve communication helps to lower heart rate, blood pressure, and to slow down other organs after a stressful experience by utilizing certain neurotransmitters like acetylcholine and GABA.
The researchers determined that mice that had the vagal connection cut were not as afraid in open spaces or to bright lights than those who had the vagal connection intact. However, those animals that showed less fear, unfortunately, had a longer retention of learned fear. A conclusion was made that an innate response to fear appears to be significantly influenced by these signals that the vagus nerve reads from the gut and send to the brain which confirms the importance of healthy vagal tone to maintain calm in a stressful situation and to overcome fear conditioning.
It is also interesting to note that the researchers found that with the loss of those signals coming up from the gut it had an impact on the production of both adrenaline and GABA. When a negative stimulus was switched to a neutral one, those rats with the disconnected gut instincts took a much longer time to realize and to associate the sound they had before to a new safe neutral situation. These findings point to exciting possibilities for the treatment of anxiety disorders and those who suffer from post-traumatic stress disorder (Bergland, 2014). While scientists may not know precisely how the vagus nerve communicates with the gut and the microbes that reside there, this experiment demonstrates that it does indeed occur.
In the study done by (Bercik et al., 2011), it was shown that when mice were given various oral antimicrobials, it altered brain chemistry independently of the autonomic nervous system, gastrointestinal-specific neurotransmitters, or inflammation. Therefore, the findings concluded that intestinal dysbiosis might contribute to psychiatric disorders, especially in patients with bowel disorders like IBS, Celiac disease, or Crohn's. This is believed to be because the vagus nerve has the ability to communicate with the microbes residing in the gut. It is believed that these bad microbes can cause poor vagal tone which would result in poor communication giving these microbes the opportunity to overrun the good resulting in poor physical and mental health. Once healthy gut flora is restored, mental health restoration can follow.
In the study done by (Foster & Neufeld, 2013), germ-free mice were compared to house-specific pathogen-free mice where the germ-free mice exhibited an underdeveloped immune system. These germ-free mice were administered food-borne pathogens that provided evidence to support that bacteria in the gut can stimulate stress through the activation of the vagus nerve. However, when healthy strains of probiotic were administered the altered environment triggered neural pathways through the vagus nerve letting researchers know that the brain can sense these gut changes and can respond accordingly. Additionally, rodent behavior was impacted by the environment in the gut as it was altered and manipulated. Table 1 below shows the summary of the impact of these manipulations on animal behavior, specifically for anxiety and depression.
It was also fascinating to learn that through a process called Fecal Microbiota Transfer or FMT where feces from a healthy specimen can be transferred to an unhealthy specimen resulting in the unhealthy individual taking on the healthy gut microflora of the donor. Dr. Dimitri Drekonja from a Minneapolis VA hospital research group uses this treatment to combat infectious diarrhea or Clostridium difficile-related diarrhea, and doctors like Russell Schierling believe that there will soon be a new way to treat those with mental health issues. He has concluded that for chronically ill individuals, probiotics cannot compete with FMT because feces contain the bacteria that make up most of a person's microbiome that range anywhere from a few hundred, to in some cases, a few thousand strains. The very best probiotics have maybe 20 strains (most have no more than a handful) and are, therefore, not very effective at all (Doctor Schierling, 2017).
In human studies, there is evidence that probiotics have similar effects on depressive and anxiety-like behaviors. In the trial where participants were given a mixture of probiotics for 30 days, the treatment group reported less distress than the control group and in another study where participants were fed a probiotic milk drink for three weeks, subjects that initially had lower scores for depressed mood demonstrated a significant improvement in symptoms after this treatment. Additionally, in yet another human pilot study, patients with Chronic Fatigue Syndrome received Lactobacillus casei for two months and showed much fewer anxiety symptoms than before. FMT in humans have been used to treat various conditions relating to infectious bowel conditions like diarrhea, IBS, and Crohn's, however, there doesn't appear to be any research being done to utilize FMT for psychiatric disorders. However, in a study published in the Journal of Clinical Psychopharmacology and Neuroscience states that this is a very real future possibility because of the strong evidence is shown in the treatment of other conditions where psychiatric symptoms are comorbid to these various digestive disorders (Evrensel & Ceylan, 2016).
With the research that is being done, a clear correlation is being shown between the condition of an individual's gut environment and their respective behavior. The prescriptions of antidepressants and other psychotropic drugs should have a different protocol, one that should first involve the analysis of the individual's gut health and a thorough investigation of the medical history to determine certain physical causes of psychiatric illness. It seems as though our diagnostic protocols are completely obsolete. Where is the personalized treatment of unique biochemistry? Are there plans for side effects to include new and different psychiatric symptoms resulting from the prescription of any drug? It seems as though conventional medicine has applied a one-size-fits-all treatment to mask symptoms without consideration for the cause of a particular health issue. Everyone should be all too familiar with the impact that anxiety or nervousness can have with the gut, because we have experienced those feelings of having butterflies, but not too many know or understand that this communication can go both ways through the gut-brain axis involving the vagus nerve.
There seem to be countless things an individual can do to promote an optimal condition in the gut when considering what exercise, diet, supplementation, and mindfulness-based stress reduction techniques can do to improve vagal function. It appears from much of the research being presented that a one disease one drug model is far too inadequate whereas a customized approach that looks at individual distinctions where a treatment plan could be made more personalized would be much more appropriate. Furthermore, there is plenty of room for education and self-help before the need should arise where a person would need to go to a specialist for additional help. This is where the findings of the FMT application is so fascinating as well as promising because it appears to work for patients with considerably serious conditions.
Going forward, there is a tremendous opportunity for health practitioners first to consider how the gut-brain axis and how dysbiosis influences mental illness. As scientists make further advancements in the understanding of the role that the microbiome has in mental health issues, the potential value of analyzing one's gut environment to reveal altered brain function and mental illness is quite exciting. The use of probiotics and treatments such as FMT need to be explored further to close the gap between theory and practice so that protocols can be changed that results in more people becoming well. Currently, the use of psychiatric drugs to treat mental illnesses such as depression and anxiety have a huge cost and is a huge financial burden on the current healthcare system in place. By adopting these complementary and alternative strategies to address various mental health issues will create the potential to improve healthcare for all.
Conclusions and Recommendations:
It is a travesty that far too many psychiatrists and psychologists fail to examine the role of gut health and mental health and the correlation of the two. It is important therefore that people are made more aware of this information and to educate themselves as well as ask specific questions to healthcare providers. Education is key to employing self-help strategies like the use of strategic supplementation with various strains of probiotics and the consumption of fermented foods. Prebiotic and probiotic foods can become more than mere nourishment but could be used as tools to be used as therapeutic treatment protocols to assist the body's own mechanisms for healing. It is important too that people are made aware of other nutritional strategies to promote the reduction of the inflammatory state and do what they can behaviorally to promote a healthy gut like exercise and stress reduction techniques.
There are various things one can do to improve vagal nerve tone like diaphragmatic breathing, humming, singing, or chanting. Cold water is said to stimulate the vagus nerve as well as certain exercises like yoga or even body massage. Studies have found that higher vagal tone is associated with greater closeness to others and more altruistic behavior. Also, anyone that understands the mental state of "Flow" or the ability to do something without really consciously thinking about it knows how to stimulate the vagus nerve. It is said that flow cannot be achieved without vagal tone influence since it is the combination of sympathetic (fight-or-flight) and vagus activation that creates the right environment for this "flow" state.
More studies are warranted to prove the efficacy of nutrition and the mind-body connection, the health of the gut, and its correlation with mental health. There needs to be a more integrative approach to mental health care one where the emergence of complementary and alternative medicine can be enjoyed by everyone in America. This is something that should not only be available to those with a higher education, holistic medical knowledge, or by those with enough money to afford these treatments that are currently not part of the typical healthcare in this country but by all. CAM treatments for mental health as well as other issues should be a part of mainstream care everywhere and offered to everyone.