Microbiome: Healthy Gut Bacteria and Adrenal Fatigue Syndrome
The microbiome is defined as the entire habitat, including the microorganisms, their genomes (i.e., genes) and their surrounding environmental conditions. The word itself is derived from the word “biome” which refers to the characteristics of an environment including abiotic (nonliving) as well is biotic (living) factors. Microbiome can easily be mistaken from another commonly encountered term called Microbiota, which is the composition of the microorganism population within a defined environment, such as healthy gut bacteria in the GI tract or organisms in the oral cavity.
An estimated 90 percent of cells found in the human body are not human after all but of mostly prokaryotic origin, derived from at least 40,000 bacterial strains in 1,800 genera. Though considerably smaller in size, these approximately 100 trillion cells weigh up to 5 pounds in an adult individual – approximately the weight of a full-grown human brain. They inhabit in all parts of the body that are exposed to the environment, such as the mouth, skin, and vagina. The biggest population resides in the gut where they have a constant supply of the nutrients necessary for their survival. Taken collectively, these organisms outnumber our human cells 10:1.
Healthy Gut Bacteria – Microbiome Development
The fetal gut is sterile and is established at birth with microbes from the mother’s vaginal and fecal microbiome as well as with other environmental microbes confronted in the first days of life. Early colonization depends on the delivery mode, diet (breastfeeding vs. formula feeding), hygiene, and antibiotic treatment. The first colonizers are facultative anaerobes, e.g., Escherichia coli and Streptococcus spp., and obligate anaerobic species, which colonize as oxygen levels in the gut decrease. A child’s microbiome stabilizes and become adult-like at three years of age. Throughout adulthood, our microbiome is in a continuous process of self-balancing to help the body maintain homeostasis.
As we grow into old age, changes in the microbiome occur, resulting in decreased microbial diversity and healthy gut bacteria, and with that, increased inflammation.
Most of the microbes in our body are not harmful at all, but rather help in maintaining processes that are necessary for a healthy body. They do not cause diseases under normal circumstances, and are deemed to be members of the normal flora or normal microbiome and part of healthy gut bacteria. Our body needs them for a multitude of functions including the carrying out of various enzymatic reaction that otherwise we cannot do, or synthesis of vitamins such as vitamin K necessary for good health.
Healthy Gut Bacteria and Metabolism
Metabolism is a term used to describe all chemical reactions involved in maintaining the living state of the cells and the organism. It is closely linked to nutrition and the availability of nutrients. Healthy gut bacteria are responsible for breaking down of the complex molecules found in some foods such as vegetables and meats. They therefore assist in our metabolism. These microbes are not only responsible for harvesting energy for themselves from the plant fibers we consume but also break down such plants into smaller molecules which our body can digest easily. A simple study in mice showed that certain bacteria are associated with metabolic derangement such as obesity. When obese mice were injected with the gut microbiome of normal mice, the obese mice lost weight completely. The reverse was also true, i.e., when normal mice were injected with the microbiome of obese mice, the normal mice gained weight. Similar studies using human twins, different in weight, with similar upbringings and identical genomes, manifested the same association between obesity and the gut microbiome showing that healthy gut bacteria does in fact play a role in weight.
Research has also shown a direct relationship between diet and the thriving of certain healthy gut bacteria microbial communities. This should be rather obvious. For instance, vegetarians have gut flora that is better equipped with breaking down of plant roughage, making otherwise the indigestible molecules such as cellulose available for humans. During the bacterial metabolism of the complex molecules, chemical signals that are released end up in our brains and can affect behavior. It is not a great speculative leap to consider that the microbes responsible for these chemical signals may be behind certain food cravings and have an effect on what we choose to eat. Clearly, the association between our microbiome and metabolism is far greater than we envisioned especially when pertaining to healthy gut bacteria.
It is interesting to note that at specific sites on the body, entirely different sets of microbes could perform identical functions for different people. For example, completely separate families of microorganisms existing on the tongues of different individuals will perform the same breakdown of sugars. So what are the functions of all of the microbes living in our bodies? The microbes benefit from a persistent, stable habitat, rich in energy from the food we ingest, and we in turn claim heat energy from the bacterial breakdown of compounds like cellulose that are indigestible by a humans healthy gut bacteria. The interaction between the human body and the microbes it plays host to is far reaching. The internal functions that go on in the body, which are essential for a healthy body, are dependent on specific microbiomes at various sites throughout the body and healthy guy bacteria. When microbiomes become imbalanced or altered, it is known as dysbiosis.
Dysbiosis can lead to systemic inflammation, which is associated with a wide array of diseases and conditions including heart disease, diabetes, obesity, asthma, and even autism. Dysbiosis is also being implicated in several inflammatory bowel related problems, notably those that are symptom based such as ulcerative colitis, Crohn’s disease. There is also a strong association with the brain, triggering irritable bowel syndrome (IBS). Each of these debilitating conditions has strong links to shifts in bacterial populations and healthy gut bacteria with in the gut.
A common cause of dysbiosis is ingestion of antibiotics that destroy symbiotic and competing strains necessary for optimum balance. When our normal microbiome is altered, our immune system can become affected negatively.
Microbiome and Immune System
Early in life, the gut microbiome play an integral role in the formation of a very strong immune system in humans, especially during our early childhood as the adaptive immune system develops. During this time, our immune system becomes accustomed to the foreign antigens in our body and develops a tolerance for such foreign antigen. Once a homeostasis is built, non-pathogenic microbes and the other harmless antigens will not provoke an inflammatory response. This is a good adaptive response to keep our body in a steady state. Over exposure to allergens, when combined with a weakened or underdeveloped immune system, can trigger inflammatory responses that is pathological, such as acute allergies, food sensitivities, chemical sensitivities, and autoimmune diseases. This concept is principally illustrated in germ-free mice, i.e., mice kept sterile throughout their life. These sterile mice are exceptionally unhealthy and have drastically underdeveloped immune systems. They exhibit undesirable traits and suffer from autoimmune diseases.
It is clear that the first gut microbiome of an infant can have a perpetual effect on his or her health. Scientists have compared babies delivered through C-section, where the newborn is colonizing its mother’s skin biome, and babies vaginally delivered, where the infant is colonizing its mother’s vaginal and gut biomes. Babies delivered through C-section have a greater likelihood of developing obesity and allergies than their vaginally delivered counterparts.
When dysbiosis occurs at the GI tract, resulting inflammation can lead to damaged mucosa. The tight junction between mucosal cells is compromised, and triggers further immune system responses. Unwanted proteins, toxins, and bacteria can more easily pass through the damaged lining of the gut and enter our systemic circulation. This is often referred to as a leaky gut. This can result in brain fog, depression, pain of unknown origin, fatigue, anxiety, insomnia, just to mention a few.
On the other hand, having a healthy and diverse gut microbiome, and thus no gut inflammation and leakiness, support a person’s immune system. Those with healthy gut microbiome tend to be physically strong and less prone to infections and recurrent illnesses. Their defense system is simply stronger.
Microbiome and the Brain
The intestinal microbiome has a strong connection to the brain. A bidirectional communication channel connecting the gastrointestinal and neural systems, also known as the gut–brain axis, coordinates the behavior of the gut microbiome with brain activity. This axis has a significant impact on brain development and behavior. It is evidenced that this extended communication system affects a broad spectrum of diseases, including psychiatric disorders, irritable bowel syndrome, and demyelinating conditions such as multiple sclerosis.
The brain can directly affect the gut microbiome, via signaling molecules discharged into the gut lumen from the cells in the enterochromaffin cells, neurons, and immune cells. The brain can also influence the enteric microbiome directly or indirectly, via changes in gastrointestinal secretion, motility, and permeability of the intestine.
The reverse is also true in this bi-directional gut–brain highway. Communication from gut microbiome to the brain can occur via epithelial–cell, receptor–mediated signaling and, when the intestinal permeability is improved, through direct stimulation of the immune cells. The disruption of the bidirectional interactions between the gut microbiome and the nervous system may be involved in the pathophysiology of chronic and acute gastrointestinal disease states, including the functional and inflammatory bowel disorders.
The gut is therefore, called our “second brain” for good reasons. In addition, many neurotransmitters, including serotonin, are made in the GI tract. Microbes normally present in the gut stimulate host intestinal cells to produce up to 90 percent of the body’s serotonin. Peripheral serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons. Microbes are needed by the EC to make serotonin. EC cells are therefore rich sources of serotonin in the gut. Without proper microbes in the gut, serotonin, also called our “feel-good neurotransmitter”, is severely compromised. Changes in levels of peripheral serotonin have been linked to conditions such as IBS, cardiovascular disease, depression, and osteoporosis.
The microbiome also has an important influence on the behavior of its host. Many nerve endings are positioned around the gut, which transmits signals straight to the brain via the vagus nerve. Metabolites and other minute molecules that are released from bacteria can influence everything from taste to mood. In fact, in a study, scientists swapped the microbiome of risk-taking mice with that of cowardly mice and their risk-aversion interchanged as well. Other studies have hypothesized that the types of food we crave, and that taste good to us, can also be commanded by the microbiome population in our guts, and may even be related to the microbiome population’s ability to make use of particular foods for energy.
Microbiome and the Liver
The liver is the body’s major metabolic clearing house. It is responsible for breaking down food, toxins, nutrients, medications, etc into smaller component parts called metabolites and prepare them for excretion as part of the body’s overall detoxification process to keep us clean internally. The interaction between the innate immune system and the intestinal microbiota during obesity or autoimmunity promotes chronic liver disease progression. There is a central relationship between the immune system, the microbiome, and liver disease initiation and progression.
Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in normally healthy gut bacteria of the intestinal microbiota. Unhealthy external factors, such as high sugar, fatty Western diet, and alcohol, can alter the homeostasis. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial toxic products across the intestinal wall into the liver, which can promote liver injury and inflammation. It is clear that the microbiome–immunologic–liver interaction plays an important role in overall health.
Microbiome and Adrenal Fatigue
The association between Adrenal Fatigue and microbiome is more than casual. Although dysbiosis is one of the most frequent aggravating factors of Adrenal Fatigue, it is often overlooked.
Adrenal Fatigue is a condition describing a weakened adrenal state of function due to stress intolerance. The primary symptoms are fatigue and lack of energy. It represents the neuroendocrine stress response by the body as it tries to overcome stress by way of the hypothalamic-pituitary-adrenal (HPA) hormonal axis. Routine laboratory tests are usually normal, and sufferers are normally sent home and told nothing is wrong by conventionally trained doctors after Addison’s Disease has been ruled out.
There are four stages of Adrenal Fatigue. In early stages (stage 1 and 2), symptoms are very mild and subtle, and are often passed over, with complaints such as sugar craving, afternoon slump, and exercise intolerance compensated by snacking, napping, and reduced physical activity respectively. Advanced stages of Adrenal Fatigue (stage 3 and 4) are much more serious and can be incapacitating, with symptoms including reactive hypoglycemia, insomnia, low blood pressure, salt craving, dizziness, heart palpitation, menstrual irregularity, depression, panic attacks, and weight loss. Some are even bedridden requiring ambulatory help.
It is well known that gut pathogens such as Escherichia coli, if they enter the gut, can activate the HPA. However, animals raised in a germ-free environment show exaggerated HPA responses to psychological stress as well. Stress induces increased permeability of the gut, especially at the tight junction which is the gap between mucosal cells that is usually hard to permeate. As the tight junction becomes more lax, toxins, bacteria, and bacterial antigens cross the epithelial barrier and enter systemic circulation, bringing cellular signals to the brain distally. Locally, mucosal immune response is activated, which in turn alters the composition of the microbiome and leads to enhanced HPA drive. It is clear that the gut microbiota must be taken into account when considering the factors regulating the HPA both locally and systemically.
Our intestinal health is therefore, directly connected to how well our brain handles stress and, ultimately, adrenal gland function. GI symptoms directly associated with advanced Adrenal Fatigue include bloating, constipation, food intolerance, gastric discomfort, diarrhea, intolerance to medications and supplements, and paradoxical reactions, just to mention a few. These symptoms usually improve as gut health is optimized.
Multiple pathways are involved on how dysbiosis can affect gut health. They include systemic GI assimilation slowdown as the body tries to conserve energy, metabolic byproduct built up due to liver sluggishness, extracellular matrix congestion, and receptor site damage. Dysbiosis is an unavoidable part of the big picture as the normal gut microbiome fails to normalize the body in its attempt to retain homeostasis when dysbiosis is rampant. Excessive inflammation appears to be a major common final pathway pathophysiologically with dysbiosis.
When faced with excessive stress, our body microbiome changes. Studies in squirrels living in a low-stress environment have shown that they harbor healthier communities of microorganisms. In the same squirrels examined two weeks later, studies have found that if stress levels increased, some bacteria that are potentially harmful also increased. The greater the stress in the squirrels, the less bacterial diversity are found, which can be an indicator of poor health.
Bad bacteria overgrowth and resulting GI dysbiosis are prominent clinical challenges as Adrenal Fatigue worsen to advance stages. It can overwhelm and reduce the good bacteria load. When the fungi and bad bacteria overwhelm our intestines, they can stimulate inflammation, which has the direct effect of damaging the gut track locally. If not resolved, systemic inflammation is part of the natural progression as Adrenal Fatigue worsens. The more bad bacteria are present, the more burden is placed on the adrenal glands to produce more anti-inflammatory hormone cortisol. Eventually, the adrenal glands become exhausted. Cortisol output starts to fall after reaching a peak. As cortisol level falls, inflammation increases. Inflammation is a silent killer. It damages the body even more, thus requiring more cortisol to help repair it. The adrenals are put to work even harder. This forms a vicious cycle that eventually crashes the body as it runs of out steam. Facing the threat of survival, the body starts an automatic shut down process of non-essential functions to converse energy. This also is destabilizing as without nutrition reserve replenishment sufficient to what is needed to fight stress, the body enters a state of negative nutritional reserve, creating a vicious cycle of ever lowering energy and ultimately a catabolic state as the body surrenders and assume low energy vegetative state as survival method of last resort. Sufferers become bedridden, with slow GI function, rampant systemic inflammation driven in part by severe dysbiosis.
The gut microbiome therefore plays a central role in Adrenal Fatigue. Modulating the gut microbiome should be considered as a therapeutic technique to adrenal fatigue recovery. Failure to restore normal microbiome lead to retarded recovery, frequent relapse, lower threshold to adrenal crashes, frequent infections, pain of unknown origin, metabolic derangements, brain fog, and depression.
Other Microbiome Related Illnesses
1. Irritable Bowel Syndrome
Functional bowel disorderliness such as irritable bowel syndrome (IBS) is defined solely by symptom-based diagnostic criteria. Abdominal discomfort or pain as well as altered bowel habits are the main symptoms of the condition. The exact pathogenesis of IBS is likely a confluence of many factors; however, there seems to be a connection between alterations in gastrointestinal flora and irritating inflammation of the gut characteristic of IBS. The gut microbiome is also important in preventing pathogens from flourishing, so an altered gut microbiome may also play a role in allowing colonies of disease causing organisms to form.
2. Inflammatory Bowel Disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are both forms of inflammatory bowel disease (IBD). These conditions include recurring chronic inflammation of the gastrointestinal tract. They are, however separate and distinct, with differentiating patterns of symptoms. Crohn’s disease is thought to result from an interaction between the gut’s microbe composition and the body’s genetics. It is defined by chronic segmental gastrointestinal tract inflammation. The symptoms of ulcerative colitis are similar, being inflammation and ulceration of the lining of the colon. It is thought that both these conditions are not the result of a single pathogen, but arise from dysbiosis of the gut changing the gastrointestinal microbiome and altering the functional environment; although the exact causes remain widely debated. Studies have found gut microbes to be correlated with development of IBD, and they are thought to be key factors in mucosal lesion formation. Despite the lack of a clearly defined etiology, the evidence points to a strong connection between gut microbial health and IBD.
3. Colorectal Cancer
The gut microbiome may also have a role to play in the development of colorectal cancer (CRC). Like IBD, no single pathogenic organism has been found for CRC, however some organisms of interest have been identified in studies. Fusobacteria was found in higher numbers in colorectal tumors in one study, suggesting a link. These tumors are often causal of, or at least associated with, persistent and chronic inflammation in the gut, which is also a risk factor for CRC. The link between microbially induced inflammation and CRC has also been highlighted in some other studies. Indeed, it has been established that microbial products can enter barrier-defective colonic tumors, trigger inflammation through a host immune response and, in turn, increase tumor growth.
Obesity is a complex metabolic dysregulation that develops from a prolonged imbalance between energy intake and energy expenditure. Although lifestyle factors, diet, and exercise contribute largely to the modern epidemic, the gut microbiome plays an important part in development of obesity.
Many studies with both mice and human subjects have evidenced strong associations between changes in the gut microbiome and the development of obesity. Some studies have shown a flourishing of the microbial genera Firmicutes along with a corresponding drawdown of Bacteroidetes populations in the gut of obese subjects. This skewing of population ratios between different microbial families disappeared after weight loss, returning to those seen in the gut microbiomes of lean individuals. This skewed Firmicutes to Bacteriodetes ratio was also observed in mice subjects genetically predisposed to obesity.
Genetic differences that can cause a predisposition to obesity include greater number of genes coding for phosphotransferase functions that increase the rate of carbohydrate processing, suggesting it may be easier for these individuals to assimilate energy from sugar rich diets.
Using fecal microbiota transplantation as discussed above, studies have been conducted to introduce microbe populations from both obese and lean mice into mice with microbe-free guts. The results suggest a causal relationship between microbiome alteration and development of obesity.
5. Type 2 Diabetes (T2D)
T2D is principally linked with obesity-related insulin resistance. However, several genetic and some environmental factors are thought to influence the condition. Alterations in the composition of the gut microbiome of adults with T2D, in relation to that of healthy controls, have been noted.
Incidence of type 2 diabetes (T2D) is rising in parallel with obesity, and the environmental factors that are linked with T2D risk include diet high in carbohydrates and altered gut microbiome. Low-grade inflammation is witnessed in T2D patients; diabetic mice and humans that have raised plasma levels of lipopolysaccharide (LPS), the membrane component of Gram-negative bacteria, which has been proved to impair glucose metabolism in mice. Germ-free mice have lesser macrophages in their adipose tissue and increased glucose metabolism compared with colonized mice.
Atherosclerotic plaques are hardened, thickened sections of the arterial wall resulting from accumulating white blood cells and adhesion of cholesterol to said wall. The thickening of the blood vessel wall is known as atherosclerosis, and is often the cause of serious health events such as heart attack or stroke. Microbes from the genera Chryseomonas, Veillonella, and Streptococcus have been detected in these plaques, and they also exist in the oral cavity and the gut. Studies have demonstrated that patients who had experienced an atherosclerotic event had higher levels of Collinsella and lower levels of Eubacterium and Roseburia in their gut microbiome than healthy control subjects did.
Mention the terms leaky gut, Small Intestine Bacterial Overgrowth (SIBO), food sensitivities, bloating, and autoimmune disease, and our mind seldom paints a picture of microbiome imbalance as a possible culprit. Yet it should be clear from the above discussion that the microbiome can play an important role in such disease pathology. While we are still in the early phases of research, evidence is mounting that symptoms associated with dysbiosis can reach far and wide, with symptoms that often appear unrelated to the microbiome. They include pain of unknown origin, rise of autoimmune conditions, food intolerance and allergies, migraine headaches, blurry vision, metabolic slowdown, insomnia, depression, anxiety, and brain fog.
Tips to Improve Microbiome
Here is the approach to regaining a healthier microbiome by reducing inflammation, improving assimilation, and restoring healthy flora.
- Avoid antibiotics. Antibiotics can actually have deleterious effects on the gut microbiome and healthy gut bacteria. Broad spectrum antibiotics are especially damaging as they inflict indiscriminate damage to swathes of microbial and healthy gut bacteria populations, and can disrupt the functional balance of the microbiome. As a result, more discerning health professionals may focus on narrow range antimicrobials as opposed to classic broad spectrum antibiotics unless there is no choice.
- Take prebiotics and probiotics as needed. Prebiotics and probiotics are becoming increasingly popular. Prebiotics are particular nutrients that help beneficial microbes and healthy gut bacteria to thrive and grow, helping to keep the the healthy gut bacteria and gut microbiome healthy. For example, fibrous foods, fermented foods, asparagus, garlic, and onion. Use of the oral probiotic cultures to restore the healthy gut bacteria and gut microbiome has led to promising results in treatment of intestinal disorders like UC and obesity. While it can be argued that oral probiotic doses do not provide enough microbial numbers to fully influence the colon populations, it may be that these microbes impose their influence through complex means, such as production of an antimicrobial or a modulation of your immune system. Researchers have also suggested that higher doses of one type of bacteria might not be as important as ingesting a variety of microbes or other healthy gut bacteria. One should not be carried away with ingesting the highest concentration of probiotics. More is not necessarily better, especially for those with Adrenal Fatigue because they can trigger adrenal crash as well as constipation and a dysregulation with the healthy gut bacteria. The ideal dosage matches the body’s need with the ability of the body to clear it out of the system once utilized.
- Focus on food components are proposed to benefit gut health: living microorganisms known as “probiotics” commonly found in such foods as yogurt, kefir, and kimchi, nondigestible carbohydrates (e.g., dietary fiber found in fruits, vegetables, and whole grains), and secondary plant metabolites such as flavonoids (found in brightly colored fruits, vegetables, and red wine), most of which contain healthy gut bacteria. Not all such food can be tolerated if one is in advance Adrenal Fatigue. Titrating the right amount is important.
- Add natural antifungal, including garlic and olive leaf extracts, to your regimen. Those with advanced Adrenal Fatigue need to be very careful as these compounds can trigger adrenal crash.
- Take more Spinach. Fresh vegetables are an important source of good bacteria. Leaves of spinach plant are estimated to harbor more than 800 different species of microbes. These are microbes that cannot be sterilized or removed from the plant by washing because they’re actually inside of it. Therefore, having access to this kind of microbial diversity through the things that we eat is probably very important for healthy gut bacteria.
- Take fermented herbs that help the liver metabolize toxic compounds to inert molecules for excretion, such as milk thistle.
- Make your diet more alkaline and plant based to increase pH of the body.
- Avoid inflammation triggers such as gluten, wheat, dairy, corn, processed food, sweets, and excessive carbohydrates. A Western style diet high in sugar and fat has less of the protective benefits of plant foods and simultaneously provoke other metabolic disruptions and contribute to gut dysbiosis and inflammation.
- Take digestive enzymes with all your meals to help with digestion. However, keep in mind that excessive enzymes can cause diarrhea.
- Take high quality mercury free anti-inflammatory omega 3 oils with high concentration of EPA/DHA.
- Fecal microbial transplantation (FMT), more commonly known as fecal transplant, is another strategy used to improve and fortify the gut microbiome. Fecal transplants from a donor individual with a healthy gut can introduce healthy populations of beneficial microbes where they may be dwindling or even absent in the GI tract of the individual receiving the transplant. For example, difficult cases of Clostridium difficile infection that seem resistant to ordinary treatment are effectively addressed by FMT, with high remission rate. Those with Adrenal Fatigue usually do not do as well, and in fact, often trigger relapse after a brief period of success if the underlying stressors are not removed.
© Copyright 2016 Michael Lam, M.D. All Rights Reserved.
Dr. Lam’s Key Question
Is there a correlation between cortisol received in the fat cells of the stomach and binge eating or cravings?
Fat cells have 4x more cortisol receptors than peripheral tissues.