In the first installment of the gut-brain series we introduced the mechanics behind the gut-brain connection; the role of cytokines, and the transport of these inflammatory messengers from the gut, via the vagus nerve, to the brain's immune system; the microglia. Simply put, this is the transport mechanism that is responsible for the sharing of inflammation between the gut and brain.
There is in fact another component of physiology that these inflammatory cytokines (IL-1, IL-6 & TNF-Alpha) interact with that effects our mental state; this being the pathway that tryptophan takes. Tryptophan is the precursor to serotonin in the brain (commonly known, and believed to be, the happiness hormone). In a non-inflammatory state tryptophan is converted into 5-HTP, which in turn becomes serotonin. In an inflammatory state cytokines stimulate the production of an enzyme called IDO (Indoleamine-pyrrole 2,3-dioxygenase), this sends tryptophan down a pathway known as the kynurenine pathway; leading to the creation of quinolinic acid, a known neurotoxin that attaches to the host of NMDA receptor sites in the brain. This has been demonstrated in studies where treatments of interferon (which induces inflammation) up-regulate the production of quinolinic acid, and result in increased depressive symptoms and severity of depression. (1, 2)
As a side note - while 90%+ of the serotonin in the body is in the gut, this serotonin does not cross the blood-brain barrier to interact with serotonin receptor sites in the brain; there are transport mechanisms for serotonin to exit the brain, but none to enter.(1, 2)
Now, while all of this is very interesting, a logical question when discussing inflammation, and its impact on our health, could be: Why do we care? What is it about chronic inflammation that exposes us to risk groups for neuro-degenerative disorders, metabolic diseases, depression and anxiety? Perhaps even, what exactly is inflammation?
This is not an answer I knew, or was even particularly worried about, when I began changing my diet and lifestyle to facilitate my personal healing process. It was something that began to interest me in the later years, as I fostered a thirst for the reason behind why I was ill, and why overhauling my lifestyle had such dramatic effects.
SO, WHAT IS INFLAMMATION?
Our body and our brain both have an immune system. The purpose of an immune system is to act as a first line of defense for the body or brain. It protects us from a variety of intruders; in the form of bacteria and viruses.
Immunologists have identified two dominant types of immune responses: TH-1 and TH-2. The TH-1 system is kicked in when we get something like a splinter; the response is immediate, surrounding the splinter with puss. The TH-2 system is a more delayed response, and the one we are concerned with now.(3) When an intruder, or antigen, is present in the body, the immune system releases antibodies that attach to these antigens (intruders). These are then selectively destroyed by the immune system to help bring the body back to a state of homeostasis. This process results in inflammation; as the natural defense kicks in, the body becomes inflamed. In the body, once the threat is neutralised, the inflammation is turned off as t-cells are released to tell the immune system to back off. As we discussed in the first installment, the brains immune system (the microglia) is harder to dampen, as there are no natural built-in mechanisms to turn off inflammation once it has been introduced; we’ll discuss this further shortly.
To make it a little less nerdy and accessible; inflammation in the gut from diet, lifestyle or stress is the result of an immune reaction; where our immune system kicks into gear to clear out an intruder that it perceives as a threat. These include environmental toxins, bacteria and pathogens, proteins in certain foods, and a by-product of the stress response.
With this understanding we can see that in a normal situation inflammation is useful to the body. It is the by-product of our body's natural immune response to a perceived threat. The issue arises when inflammation goes unchecked, cannot be turned off and is constantly being activated unnecessarily. As is the case with autoimmune diseases, depression and anxiety, in the cytokine model. Autoimmunity occurs when antibodies released by the body not only bind to the protein threat (antigens) but they also bind to the body’s own tissues.(4)
With autoimmune diseases playing such a big part of chronic disease right now, it's quite obvious that our present way of living is out of alignment with our natural predisposition.(5) We’ll go into this further when we discuss the impact of gluten and other inflammatory foods in our diet.
INTESTINAL PERMEABILITY OR 'LEAKY GUT'
This immune reaction goes hand in hand with permeability of the gun lining; the job of the gut lining is to prevent unwanted proteins, bacteria and pathogens from entering the blood stream. Intestinal permeability (the loss of the gut linings' integrity) is commonly known as ‘leaky gut’. The resulting inflammation in the gut triggers those cell signalling messengers, cytokines, to travel through the GI tract via the vagus nerve and turn on inflammation in the brains immune system (the microglia). From here we observe the occurrence of something called ‘leaky brain’, where the mesh that protects your neurons from pathogens (the blood-brain barrier) is broken down. (6)
If you commonly experience gas, bloating, constipation, diarrhea, or have a gluten sensitivity; it is highly likely you have gut permeability. If you commonly experience brain-fog - where you find yourself in a state of mental fog, with resulting memory recall issues and inability to focus; your brain is inflamed and it is highly likely your blood-brain barrier has been compromised.
CAN BEING STRESSED OUT CAUSE INFLAMMATION?
Another important component to the management of inflammation is cortisol, which mediates inflammation in the body. Without adequate cortisol, inflammation is free to run unchecked in the body. This is something we see occurring in people with low cortisol; through diet and lifestyle the cortisol reserves are depleted from repeated releases of cortisol from the adrenals (stress). Cortisol, while beneficial, can also be neurotoxic; it is thought that the brain turns off the release of cortisol as a method of self-preservation. When this occurs inflammation is no longer mediated through this mechanism, and a resulting chronic inflammatory state is experienced. (7)
DEPRESSION, THE GANG AND INFLAMMATION
It’s very rare that depression stands on its own. By looking at the accompanying symptoms we can begin to hone into the root cause of the depression, and understand the role inflammation plays. The most common friends of depression are: anxiety, insomnia, and fatigue; in more rare cases we also see the presence of some form of psychosis.
DEPRESSION & ANXIETY
In the case of depression and anxiety it is often that the brain and hormonal system are fatigued by the inability to shift the balance between the parasympathetic and sympathetic nervous system. The root of this often lies in a combination of physiologocial and external factors. The presence of an un-balanced microbiota (the bacteria that live in our gut), autoimmunity (GAD, hormonal or the nervous system), or depleted cortisol reserves from psycho-social stress can all result in the physiological expression of depression and anxiety. (8)
DEPRESSION & INSOMNIA
In the case of depression and insomnia it is often that one’s cortisol circadian rhythms have been thrown off. Cortisol’s natural rhythm should be one that is high in the morning but low at night. If this rhythm is out of whack one may find themselves wide awake at 3am, and fatigued throughout the day. There are a variety of expressions of cortisol balance issues, depending on the stage and length of time one has been experiencing chronic stress. Where one individual may have very high cortisol, another may have their reserves highly depleted from months or years of chronic stress. Both will experience insomnia but the specifics of the symptoms and root cause will differ. (9)
DEPRESSION & FATIGUE
In the case of depression and fatigue we are borrowing from most pairings and introducing some new elements. An individual may have hormonal imbalances causing the fatigue, with roots in thyroid autoimmunity for instance; they may also have an unbalanced microbiota due to chronic inflammation or infection; adrenal fatigue from prolonged cortisol release may be another; a metabolic issue such as blood sugar imbalances or iron deficiency; finally brain based fatigue from neurological autoimmunity or chronic inflammation. (10, 11, 12, 13)
It is important to remember that these root cause elements often move between each pairing; sometimes people will experience all of the pairings and the root cause will be one or two elements; other times someone may experience one pairing yet an element from each. Often these symptoms blur into each other as physiological and neuro-degeneration occur.
TO INFLAME OR NOT TO INFLAME – CHOOSE YOUR FOODS
As we have spoken about there are groups of foods that aggravate the immune system, causing an inflammatory response. These are: sugar, dairy, gluten, processed foods, GMOs, and grain based carbs. For the most part, our bodies simply have not adapted to these new proteins, which for a lot of us result in an inflammatory response that can lead to a further autoimmune response. Many people go on with undiagnosed sensitivities to these foods, and present with symptoms of a variety of chronic diseases for years; sometimes decades.
Gluten is a particularly interesting one that is worth discussing; it also provides a poignant example of how an inflammatory and autoimmune response can escalate and cause an array of health issues. The protein in wheat, known as gluten (or more appropriately gliadin), has demonstrated to be cross reactive with body tissue. This is something called ‘molecular mimicry’ and occurs when the amino acid sequence of two proteins are so similar that the immune system cannot differentiate between the two, and ends up tagging the protein and your own body tissue to be destroyed. (14, 15, 16, 17)
Remember how we spoke about the body producing antibodies that attach to an antigen (such as gluten), then the immune system destroys the antigen? In people who have gluten sensitivities, the body releases antibodies to gluten that are so similar to body tissue that they attach to both. The immune system then destroys the antigens and attacks the tissue of the brain and body at the same time.
WHY GLUTEN, NOW?
Often the question is asked as to why we have such high occurrence of gluten sensitivity and coeliac disease compared to previous times in history. It is through modern agriculture processes that gluten today is not what it used to be, and the reason we are seeing such a steep rise in gluten sensitivity. Broadly speaking these can be attributed to the practice of combining multiple strains of wheat - called hybridisation; and deamidation, where acids are used to make gluten more water soluble so it can easily mix with other foods. (18)
THE FIRST STEP
It is important to remember that while disease may be complicated, health does not have to be. If you ever feel overwhelmed with information, remind yourself that engaging your own intuition is of primary importance to achieving optimal health and wellness. It is absolutely possible to achieve fantastic results without understanding any of the complex mechanisms responsible for the outcome. So while I personally may get kicks from diving into the depths of this information; you may just want to recover your health, or optimise your well-being, without becoming professor health-nut. This can be done by addressing your nutrition and lifestyle, and tailoring this to your desired outcome.
If you are experiencing sub-optimal health that encompasses any of the symptoms mentioned above, the first (and perhaps most important) step you can take is to consider your diet and lifestyle choices. Remove inflammatory foods from your diet and include nutritional support to assist in the reduction of inflammation and restoration of your microbiota.
As I have mentioned on my blog previously, introducing turmeric to your diet is a must for anyone wishing to curb inflammation; as is including fermented foods (such as kefir, kombucha and sauerkraut) to rebalance the microbiome. We now know that we can re-balance our microbiota dominance (balance of good-bad bacteria in the gut) in 72 hours with dietary changes alone (19); making just these simple changes will provide a tremendous step towards health and happiness.
*Always work with a trusted health professional to guide you as you incorporate these changes
Soon I will be releasing a nutritional plan to facilitate healing of the body, and more specifically, the mind. I find it somewhat alarming that there is so much focus on aesthetics, and very little dietary information provided regarding our mental well-being. In my experience the body will follow the mind, and as we put plans in place to nurture the mind, we will also find ourselves transforming the body, including its aesthetics, in tandem.
As always, offer love and support to those around you, even if they haven’t voiced any issues. This can be as simple as offering to listen, from a gentle space of unconditional understanding and acceptance. Facilitating a paradigm shift in the world of mental wellness, starts with offering love and compassion to the person sitting next to you.