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In-Depth Article on Microbiome Gut Brain Axis

Your microbiome exists symbiotically in your gut to enhance gut function, stabilize the gut environment, and even perform functions your gut can't do!A human body contains over 10,000 microbes — or more than ten times the number of human cells! The genome of the microbiome, as an entity, is 100 times larger than the human genome, implying that the majority of genetic material inside your body is not actually yours, but the microbes’. These microbes include viruses, fungi, and bacteria that use the body as a habitat to form a balanced ecosystem. This ecosystem is called the microbiome, which is found in and on the bodies of humans and living things—in the mouth, on the skin, inside the gut. The human microbiome includes both harmful and beneficial organisms. The balance is shifting constantly and can affect the human host’s health. For the most part, the bacteria found in your body are valuable to your health and well-being and play a vital role in your survival. These bacteria are not only depended on for survival, they assist in the daily functions of digestion, vitamin creation, and protection against infections, as well as in a plethora of other roles. This article primarily deals with the gut flora, those microorganisms that live in the digestive tract.

The NEM Stress Response

The neuroendometabolic (NEM) stress response is the body's system of dealing with stress. There are six major components or circuits, each comprised of various organs and systems programmed to act on specific, targeted anti-stress responses. These components work synergistically to ensure that your body is well taken care of in the face of stressful situations. The neuroaffective and inflammatory responses are two circuits within NEM stress response that significantly alter mood, immune function, and cognition. These circuits involve three intricately interconnected components—the gut, brain, and microbiome—forming what is called the gut-brain axis. What happens to one component will affect the others. The neuroaffective circuit is made up of the autonomic nervous system, central nervous system, and gut. The inflammatory response circuit is composed of the gut, microbiome, and immune system. As you can see, the gut and its microbes are important to both circuits and link the two. The brain and gut seem so different and so far apart, so how does the connection work? Let’s take a look.

The Gut-Brain Axis

Gut flora influence various brain functions, affecting your thoughts, emotions, and memory. Three quarters of the body’s neurotransmitters are actually made in the gut. That is why the signals that go between the brain and the gastrointestinal (GI) tract are vital to establishing and maintaining homeostasis, immune health, and hormonal levels. This connection is regulated by the central nervous system and the enteric nervous system. When there is a disturbance in either of these systems, it affects your ability to respond to stress and influences your overall behavior. As can be seen in those with inflammatory bowel disorder (IBD) and irritable bowel disorder (IBS), there is a strong correlation between anxiety and gastrointestinal disorders that demonstrates the significance of the connection axis between the brain and GI tract.

There is also mounting evidence suggesting that the enteric microbiome (in the intestines) affects gut-brain communication, hence the naming of the microbiome-gut-brain axis.

Your gut flora - making up the gut microbiome - can heavily influence the signals the gut sends to the brain.An unbalanced collection of gut flora (dysbiosis), combined with stress, could lead to damage the gastrointestinal lining and increase the permeability of the blood-brain barrier. Thus, an unbalanced population of gut flora can contribute to the inflammation of the whole body in addition to affecting the neuron signaling from the gut to the brain.

How Microbiome Affects the Human Brain

There is a wealth of evidence that demonstrates complex interactions between host and microbe. There are three particularly important methods by which the microbes in your gut interact with the brain: directly, via the vagus nerve and a network of nerves that wrap around the gut and transfer signals to the brain; through the circulation of primed immune cells that exist in the gut and move towards the brain; and through metabolite molecules, produced by gut microbes, that enter first the bloodstream and then the brain and eventually affect behavior. These metabolites have been shown to cause abnormalities associated with anxiety and autism when injected into healthy functioning mice. This could lend further support to the possibility of microbial molecules connecting the brain, gut, and neuroaffective circuit of the NEM stress response system.


There is currently no perfect standard for a healthy intestinal microbiome. Due to environmental and genetic considerations, there are considerable differences in people’s “normal” gut flora. Generally, microbes that are healthy and diverse help to promote gut health and to maintain metabolic, structural, and signaling functionality. However, the gut can become imbalanced in a variety of ways; in particular, the term dysbiosis involves a change away from the normal diversity and stability found in the gut microbiome. This presents with an unstable gut that is unable to function normally and may eventually lead or contribute to neurological, metabolic, or autoimmune disorders. Causes of dysbiosis include environmental toxins, alcohol intake, excess stress, and overgrowth of yeast and bacteria.

For those with Adrenal Fatigue, high stress levels can often lead to dysbiosis. In addition, since your body is in a low energy state, the gut (and other bodily functions) often slows down in an effort to conserve energy. As your gut slows down, food stays in your stomach longer, resulting in reduced assimilation, longer transit times, and increased inflammation, as allergens have more time to seep into the body through the gut. If the food stays in the gut for a prolonged period of time, it can even start to rot in the stomach, releasing toxic compounds into the stomach. This may be another cause for gut dysbiosis.

Leaky Gut and Inflammation

Stress from the environment, relationships or other sources affect the balance of your microbiome causing dysbiosis and breakdown of normal gut functions.When the mucosal lining of the gut fails in its role as a barrier to protect against potentially damaging molecules that can enter the blood flow, the resulting condition is known as leaky gut. Lipopolysaccharides on the outer membrane of gram-negative bacteria can then be found entering the bloodstream, prompting an inflammatory response. Inflammation influences the brain in several ways and is thought to be a major contributing factor to depression. In fact, selective serotonin reuptake inhibitors (SSRIs)—one of the main classes of drugs used in depression treatment—has been found to reduce inflammation in the brain. This anti-inflammatory effect may be an important part of why the drugs are effective. Thus, it is easy to see how your gut can have a major affect on the neuroaffective circuit and your mood simply through an elevation or reduction of inflammation.

Increased permeability of the intestinal lining can also lead to food allergies, malabsorption, and toxic overload. There is a saying that a leaky gut leads to a leaky brain, as the buildup of toxins can cause changes in mood, depression, fatigue, poor memory, confusion, and anxiety.

Unfortunately, the details of these connections are difficult to study because every individual’s gut microbiome is unique, and the terms healthy and unhealthy are in reference to an individual’s specific state of normality.

Gut Flora and Neurological Disease

Disturbances in the gut — such as an alteration in the composition of the microbiome — have been linked to neurological disorders such as multiple sclerosis (MS), Parkinson’s disease, and autism spectrum disorders. A Parkinson's patient’s first symptom is usually constipation; the second is often the loss of taste and smell. These gastrointestinal disturbances are present long before the symptoms of motor neuron dysfunction, such as tremors or a shuffling gait, appear.

Multiple environmental risk factors for neurological conditions have been found to promote an immuno-inflammatory response. In particular, improper folding and aggregation of proteins within the brain is a possible etiology for several neurodegenerative disorders. This could be caused by inflammation in the gut triggering inflammatory effects in the brain that cause misfolding of proteins and degeneration of neural cells.

Gut dysbiosis and inflammation have also been linked to autoimmune disorders. Western nations present with higher rates of multiple sclerosis and also tend to share similar dietary habits. These diets are thought to cause inflammation and disruptions in the optimal functioning of gut microbes. Patients with Parkinson’s disease and MS both have increased numbers of antibodies to a variety of antigens and lipopolysaccharides due to a more permeable intestinal lining. Taken together, the evidence indicates that a dysregulated inflammatory response circuit can be the result of prolonged stress, among other factors.

Alzheimer’s disease and general cognitive decline are marked by changes in the brain, disruptions in immune function, and increasing oxidative stress. These factors are all shaped by diet and gut flora in animal experimental models. One important link involves a neurotrophin, a type of protein that is responsible for the protection and the encouragement of healthy neurons. The production of this neurotrophin is dependent on the gut bacteria, and declines in individuals with Alzheimer’s. Changes to the microbiome occur with age and can be linked to neurodegeneration.

Gut Flora and Psychiatric Disorders

The connection between the gut and the brain mean that the microbiome has a strong influence.The connection between the gut and mental health has garnered increasing attention in recent years. Various psychological disorders, especially depression, may actually be disorders of inflammation, with the gut being a crucial mediator. Several animal studies have demonstrated that transplantation of microbes from anxious or depressed mice to germ-free mice could induce the same behaviors in the previously healthy mice.

Anxiety and depression are also common symptoms of Adrenal Fatigue. It is therefore vital for those suffering from Adrenal Fatigue Syndrome to keep the microbiome healthy. This will help to restore balance to the neuroaffective circuit, calming the body down and enabling a speedier recovery.

Promoting Healthy Gut Flora: Strategies

It's not only you that is nourished by what you eat, but gut flora as well. Use healthy foods to promote a microbiome dietIn those with psychiatric or neurological conditions, it is difficult to determine which came first, the disorder or the unhealthy gut. Dysbiosis of the gut could account for both, but so could stress. It is also important to consider the environmental risk factors—such as an unhealthy diet and lifestyle—that may upset the health of both the gut, gut flora, and brain. Promote healthy flora in your gut with a microbiome diet.

It is clear that neurological/neurodegenerative and psychiatric disorders share similar causes and symptomatology, as well as a common underlying pathophysiology of an unhealthy gut that influences numerous intersecting pathways on the microbiome-gut-brain axis. However, it is difficult to determine the function of these individual systems separately. The entire microbiome-gut-brain axis is therefore still poorly understood.. For brain conditions, the gut could prove to be the missing piece of the puzzle, providing new understanding of the etiology in ways that might support the introduction of new public health and clinical interventions.

The composition of the gut microbiome is quite resilient and adaptable. The key factors that are essential to its stability and diversity are all components of lifestyle. Several strategies for improved gut health, and in turn brain health, are given below.

Microbiome Diet

Diet plays an important part in determining the amount of each type of bacteria and the phylogenetic diversity of gut flora. A healthy diet of vegetables, fruits, and a variety of whole grains, will help the population of Bacteroidetes. Bacteroidetes are particularly useful in the production of short chain fatty acids (SCFAs), which assist in the regulation of gut inflammation. Large amounts of SCFAs tend to decrease intestinal pH and prevent growth of some pathogenic bacteria such as E.coli and Enterobacteriaceae. SCFAs also help curb appetite; they attach to the receptors in the gut and regulate the hormones for appetite control. Thus, the microbiome and its production of SCFAs may play important roles in dietary intake, rate of fat deposition, utilization of fat, insulin resistance, and diabetic inflammation. Vegan and vegetarian diets also increase phylogenetic diversity of the gut flora compared to diets that include meat.

Body weight in mice can be affected by the transplantation of microbes in the cecum (the beginning of the large intestine). In one study, genetically obese mice had significantly less Bacteroidetes and more Firmicutes relative to their lean counterparts; but in another, when the gut microbes of a lean mouse that had undergone gastric bypass surgery were transferred to germ-free mice, those mice experienced weight and fat loss. These studies showed that dietary patterns that favorably alter the gut microbiome—specifically those that emphasize plant-based foods—might have significant benefits to human health and confer greater resilience and adaptability to change.

There are three food components that are largely thought to promote gut health:

  • Probiotics, living microorganisms that can be found in consumer goods such as yogurt and kimchi,
  • Non-digestible carbohydrates, such as fiber commonly found in vegetables, whole grains, and fruits,
  • Secondary plant metabolites, especially flavonoids found in red wine and brightly colored fruits.

Individuals who adopt what’s known as the Standard American Diet (SAD) experience fewer benefits of plant foods, while simultaneously provoking disruptions of other metabolic functions by eating large quantities of processed sugar and fat. These two aspects of the SAD both contribute to the development of gut inflammation and dysbiosis.

Prebiotics, Probiotics, and Fermented Foods

The gut flora boosting power of prebiotics, probiotics and fermented foods can be good microbiome diet optionsPrebiotics fibers that are not digestible by your gut enzymes. They are usually fermented in the GI tract by bacteria and selectively stimulate certain intestinal flora and metabolic activities. Probiotics are foods that contain helpful microbes that are able to survive stomach acid and bile; they enter the intestines and adhere to the lining, growing and establishing temporary residence in the intestines.

There is evidence to suggest that prebiotic and probiotic supplements and fermented foods are beneficial for the gut. The digestion of fermented fibers has natural anti-inflammatory effects. Fermentation of food makes it more digestible, turning polyphenols into an active state. It also produces more vitamins, enzymes, and amino acids while breaking down phytates, tannins, and oxalic acid. An additional benefit of fermented food is, of course, the lengthened shelf life.

Probiotics and Behavior/Central Neurotransmitters

Since 90% of neurotransmitters are made in the gut, it makes sense that gastrointestinal conditions can influence mood and behavior. Irritable Bowel Syndrome (IBS) is found in 10-20% of adults in the US, and they have much higher rates of anxiety and depression than the background population. Studies have shown that probiotics are beneficial in the treatment of both the GI symptoms and anxiety and depression, in those affected. There is mounting clinical evidence for probiotics reducing stress and anxiety responses, as well as for improving the general mood of IBS patients who suffer from chronic fatigue. Studies have assessed the effect of a mixture of Bifidobacterium longum and Lactobacillus helveticus on human subjects and rats showing that anxiety was reduced. Although the mechanism of action is still to be determined, some probiotics seem to lower inflammation, decrease stress from oxidation, and improve general nutrition.
Specific probiotic strains can assist in the modulation of various facets of the microbiome-gut-brain axis. However, it is important to note that these effects vary from organism to organism and individual to individual. Nevertheless, the data strongly suggests that probiotic strains have great potential to bolster the gut flora and thus regulate behavior and the brain.


Exercise may diversify the gut flora. Athletes had increased bacterial diversity in the gut and fewer indications of inflammation compared to non-athletes. Researchers found that individuals who participated in moderate exercise more than 30 times a month presented with escalated levels of brain-derived neurotrophic factor (BDNF), compared to individuals who either didn’t exercise at all or exercised at an extreme level. BDNF promotes anti-inflammatory pathways and leads to the promotion of both brain and gut health.

When Strategies Do Not Work

The above strategies will work well for most healthy people. You should be more cautious, however, if you suffer from certain conditions such as:
If you have certain bacterial infections such as Lyme disease or Candida, a microbiome diet may help

  • If you have Small Intestine Bacterial Overgrowth (SIBO) or a systemic infection, such as Lyme Disease and Candida, fermented foods or supplements may actually makes the overgrowth worse, leading to bloating, flatulence, and pain.
  • If you have Inflammatory Bowel Disease (IBD), enzymes supplements may trigger inflammation in certain people.
  • If you have Irritable Bowel Syndrome (IBS), excessive exercise can trigger constipation and fatigue.
  • Excessive enzyme supplementation may lead to diarrhea. The proper blend of digestive pancreatic enzymes should be considered for the clinical setting.
  • Excessive probiotics may lead to constipation. The largest number of beneficial bacteria is not always the best. In fact, it can often lead to brain fog, bloating, fatigue, and anxiety. The primary focus should be finding the proper amount to match the body’s ability to assimilate the metabolites.
  • Excessive fermented food in a body that is already congested can lead to brain fog, anxiety, and depression.

The weaker your health is, the more careful planning you will need to use with these rebalancing strategies due to other conditions that are often preexisting, such as liver congestion, extracellular matrix pollution, receptor site damages, and hypersensitivities. This includes most Adrenal Fatigue, chronic fatigue, and those struggling with advancing cancer. Always consult a knowledgeable and experienced healthcare professional, because the wrong approach can worsen your condition quickly.

Microbiome Diet Summary

Since the microbiome plays a major role in the gut-brain connection, gut flora can be used to alter the neuroaffective and inflammatory circuits of the NEM stress response system. The connections are so complex and numerous that much more research needs to be done to explore these mechanisms and individual variations. In the meantime, however, consider using prebiotics or probiotics in your recovery plan to promote optimal gut and mental health.

Dr. Lam’s Key Question

When you feel bloated after eating cheese, it may be that your digestive system is missing the enzymes to digest lactose. Taking digestive enzyme may help or specifically lactase.