How hormones and gut health impact your immune system

Our immune system has become more important than ever due to this unprecedented time. It’s natural to want to learn more about ways that you can boost your immune system or whether your underlying condition puts you at increased risk for the virus symptomatology.

With this article, my goal is to offer you a new perspective on immune health. One that comes from an understanding of the relationship between your hormones and immune system, and perhaps more importantly, the relationship between your gut and immune system.

Before I dive into the science, I want to explain a few immune concepts and definitions that will come up again later in this post:

1. Our immune system is primed to respond to antigens. Antigens are foreign substances that can trigger our immune system. This includes pathogens, food particles, and other toxins and chemicals.
2. Our immune system has two branches: the innate immune system and the adaptive immune system. The innate immune system is our nonspecific defense mechanism that kicks in almost immediately or within hours of antigen exposure.
3. Our adaptive immune system, on the other hand, is our second line of defense. Unlike the innate immune response, the adaptive immune response is specific to only one antigen. The adaptive immune response can secrete chemicals to destroy this single antigen directly or secrete antibodies to enhance phagocytosis (a process by which the antigen involved is engulfed and destroyed). Adaptive immunity also involves a “memory” feature that provides us with long-term protection from reinfection. Upon re-exposure, this memory mechanism allows our immune system to quickly retaliate.
4. While the adaptive immune response is specific to one antigen and incredibly powerful, sometimes it can make errors and attack itself (the host). When this happens, autoimmune diseases (i.e., Hashimoto’s, Lupus, Rheumatoid Arthritis) can occur.

How hormones play a role

Cortisol

Cortisol is our body’s natural stress hormone. It’s released from the adrenal glands in response to normal events such as waking up in the morning and exercising. Acute bouts of stress prompt cortisol’s release, which have far-reaching and widespread effects that then allow the body to carry out numerous biochemical processes and maintain homeostasis. One of its main functions is to ensure that our blood sugar levels are optimal. When we experience a stressful episode, cortisol floods the body with glucose and gives us the energy we need to “fight-or-flight” the stressful situation. This is a critical and much needed process in the body.

So, what’s the problem? Our hectic, fast-paced, and suboptimal diet puts chronic stress on our bodies everyday, which in turn, causes a constant release of cortisol. Chronic cortisol then begins to suppress the immune system. This can lead to increased colds and flus, increased risk for cancer, increased food sensitivities, and increased likelihood of developing an autoimmune condition.

I’m sure everyone can relate to this phenomenon. If you think back to a time you were especially stressed, what happened? Did you end up catching a cold? Were you unable to tolerate certain foods and end up having excess bloating at that time? Did you end up with an autoimmune diagnosis? It’s not hard to believe that stress directly impacts our immune system.

If we continue to experience this chronic stress over an extended period of time our adrenal glands will eventually become taxed and will be unable to continue releasing adequate amounts of cortisol. This lack of cortisol is frequently referred to as “adrenal fatigue”, and  more appropriately known as HPA axis dysfunction. Remember cortisol has the ability to suppress the immune system. And without cortisol, the immune system can overstimulate.

Research has shown that adrenal fatigue is associated with the development of an autoimmune condition or a worsening of autoimmunity (1). In my practice, if I am working with an individual who presents with an autoimmune disease, I always run the DUTCH Plus Test to help me understand the state of their adrenals. This is because in order to achieve remission, it is critical to re-establish a healthy adrenal response.

Thyroid hormones

The immune effect on our thyroid gland has been widely studied. Nearly 90% of hypothyroidism cases are actually immune mediated, meaning the underlying cause for 90% of hypothyroidism cases is actually Hashimoto’s thyroiditis. Interestingly enough, growing evidence suggests that there is actually a bidirectional relationship between our thyroid hormones and the immune system. The evidence indicates that our thyroid hormones help to modulate our innate immune response (2).

Some research is beginning to show that increased thyroid hormone, or a hyperthyroid state, can amplify the immune system’s pro-inflammatory response. What this means in terms of disease progression is yet to be seen (2). Similarly, decreased thyroid hormone, or a hypothyroid state, also continues to be under investigation. This is very much an emerging area of research, and one that I am closely monitoring and hope to write about in the near future.

Estrogen

Surprisingly, estrogen, our master female sex hormone, has actions that extend far beyond reproduction. Estrogen acts on every single cellular component of the immune system. In fact, females have higher activation of both their innate and adaptive immune systems compared to males, likely to protect them from infection during pregnancy, delivery, and postpartum. While estrogen equips the female body with potent anti-inflammatory effects, this enhanced immune protection comes at a cost. Research confirms that women are significantly more prone to developing an autoimmune disease compared to men (3).

So what about hormonal diseases, and how do these conditions impact the immune system?

There is one study from 2016 that is worth highlighting. This study explores the relationship between PCOS and the immune system. These researchers found that low levels of progesterone, which is often the case in PCOS, can overstimulate the immune system and trigger the production of even more estrogen. Further, they found that this excess estrogen was associated with various autoantibodies such as anti-nuclear (ANA) antibodies, which is the autoantibody for systemic lupus erythematosus, and anti-TPO, which is the autoantibody for Hashimoto’s thyroiditis.

It is not uncommon for women with PCOS to have other conditions, namely autoimmune diseases, as illustrated by this example. The study concluded that PCOS may have an autoimmune origin in and of itself, and that once a female is diagnosed with PCOS, they should be further evaluated for other autoimmune conditions (4).

Gut health is important too

Research on the gut microbiome and its influence on the immune system has skyrocketed over the past two decades. Scientists have confirmed that over 70% of our immune system is actually located in the gut. Even more importantly, it’s critical to continue nurturing our gut so that we can establish a strong innate immune system. In fact, studies have shown that an impaired interaction between our gut microbiome and the mucosal immune system is associated with the development of inflammatory autoimmune conditions such as inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus (5).

The transition from a healthy gut microbiome to dysbiosis, or the state of an imbalanced microbiome, is the underlying root cause of many chronic illnesses today. While much of our microbiome is dictated at birth by delivery method (vaginal vs. c-section) and feeding type (breastfed vs. formula fed), our microbiome is in constant flux throughout our lifespan. It is possible to alter the state of our microbiome through dietary and lifestyle interventions.

Next we’ll walk through the three main concepts of gut health and its relation to our immune system: 1) intestinal permeability, 2) lipopolysaccharides, and 3) short-chain fatty acids. It should be noted that while most of this post uses the term “microbiome” to describe the bacteria in our gut, our gut ecosystem actually comprises many other species such as fungi, parasites, and worms. When I consult with a client, we run comprehensive microbiome testing that assesses for all of these microorganisms as they too can affect our overall immune response.

It’s also important to note that while a percentage of my clients may experience gastrointestinal symptoms such as gas, bloating, diarrhea, and constipation, many clients will not exhibit any of these GI symptoms yet still have autoimmune symptoms. The concepts that I describe herein, such as intestinal permeability, can occur independently of these GI symptoms.

Intestinal Permeability (a.k.a “Leaky Gut”)

The intestinal gut lining is the barrier that separates the host from its environment. When this lining becomes compromised, it becomes permeable or “leaky” and allows the passage of antigens (i.e., foreign toxins, food particles, and bacteria) to enter the bloodstream. This phenomenon is known as intestinal permeability, or “leaky gut.” Intestinal permeability is directly associated with the development of autoimmune disease. The three most common triggers that can induce intestinal permeability include gluten (derived from wheat and wheat related products), environmental chemicals, and toxins that are released from pathogenic bacteria. In order to heal a leaky gut, it’s important to remove all of the offending triggers (6).

Because gluten is a known trigger for intestinal permeability, I always encourage my autoimmune clients to remove gluten from their diet. Many times, a more intensive elimination diet may be necessary but the removal of gluten is an important first step. I also educate my clients on living a non-toxic lifestyle. This involves taking an inventory of all household and personal care products and swapping these out for non-toxic products.

Many times when dealing with autoimmunity, it’s not enough to only remove gluten from the diet and switch to a non-toxic lifestyle. It’s also important to evaluate the gut microbiome since bacteria derived toxins can trigger leaky gut as well. My preferred microbiome test is the GI MAP by Diagnostic Solutions. This test relies exclusively on PCR technology to detect parasites, bacteria, candida, and more by targeting the specific DNA of the organisms tested. More specifically, this test helps to identify the pathogenic bacteria in the gut that are responsible for releasing toxins into our bloodstream, also known as lipopolysaccharides. Their assays ensure that the sensitivity and specificity is high. In other words, you can ensure that the results are accurate.

Lipopolysaccharides

What are lipopolysaccharides exactly? Lipopolysaccharides (LPS) are toxins that are present in the outer membrane of pathogenic bacteria and are released when the cell breaks down. Another term for lipopolysaccharides is endotoxins (these two terms are interchangeable). LPS toxins are directly capable of triggering intestinal permeability.

Once the gut lining is permeable, LPS can directly interact with the immune cells that are lining the other side of the gut wall. Upon interaction with LPS, these immune cells go on to initiate an inflammatory response. This inflammation will persist until the trigger is removed. Prolonged inflammation, in turn, will cause greater intestinal permeability, which will allow more LPS to enter the gut epithelium and cause further immune system activation. Over time, this vicious cycle can promote the development of autoimmunity (7).

This is the exact reason I encourage all my clients to run the GI MAP by Diagnostic Solutions. This test will tell me if pathogenic bacteria (that are known to release LPS) are playing a role in my clients’ autoimmunity. This is a true representation of a functional medicine approach to autoimmunity.

Short-Chain Fatty Acids

It’s difficult to write about gut health without discussing the importance of short-chain fatty acids (SCFAs). As our knowledge of the gut microbiome has expanded, the conversation has evolved from exclusively talking about intestinal permeability and LPS to finally bringing to light the significance of SCFAs.

What exactly are SCFAs? SCFAs are active microbial metabolites that can positively modulate the immune cells that are found in the intestine and other tissues. SCFAs are generated by beneficial microbes in the gut after fermentation of dietary fiber. Studies in mice have confirmed that increasing circulating levels of SCFAs actually decrease the risk of developing allergies, type 1 diabetes, and rheumatoid arthritis. The opposite is also true where the lack of SCFAs increases the risk of developing various autoimmune, metabolic, and inflammatory disorders (8).

The production of SCFAs is dependent on the continuous intake of diverse plant fiber. While we all know that eating vegetables is important for our health, this new research on SCFAs gives us the exact mechanism by which the vegetables we consume go on to feed our beneficial microbes, which in turn help us by producing SCFAs. This is a true symbiotic relationship.

How to strengthen your immune health by supporting your hormones and gut health

While everyone is of course different, there are some general tips and tricks that tend to work for my clients. Here are five ideas for you to experiment with:

• Have a morning routine and prioritize other stress relieving activities throughout the day. To help boost your adrenal function, it’s important to start your morning right. If upon testing my clients present with low cortisol, I always recommend they start their day with light exposure. This could mean opening up all of your curtains as soon as you wake up, getting outside for 5-10 minutes first thing in the morning, or using a lightbox during the cold winter months. I also suggest following a meditative practice everyday. This could include journaling, yoga, or using a meditation app. Light exposure and meditation-based practices help to boost adrenal function, which in turn can help to put autoimmune disease into remission.

• Try removing gluten, dairy, and sugar from your diet. These foods are inflammatory in nature and are associated with bloating, hormonal imbalances, and autoimmunity. If you feel your stomach and digestion feels better without making these a part of your daily diet, it’s likely that your immune system is also happier.

• Eat primarily a whole foods plant-based diet. This is essentially a paleo approach that includes tons of unprocessed fresh foods such as fruits and vegetables, healthy fats, and a palm sized serving of wild-caught, pasture-raised, or grass-fed meats. The majority of your plate should be filled with vegetables.

• Speaking of vegetables, I recommend eating 6-9 cups of vegetables per day. Fiber is so important to our health. The fiber from these vegetables can bind to excess estrogen and help to remove this hormone from circulation. Fiber can also feed the beneficial bacteria in your gut, and in turn, produce health promoting SCFAs.

• Add fermented foods such as sauerkraut, kimchi, and coconut yogurt to your diet. These natural probiotics can help to boost the beneficial bacterial population in your gut, and in turn, help heal intestinal permeability as well as produce more SCFAs. And remember, if you take care of your gut, you will take care of your immune system.

Conclusion

If you’re struggling with hormonal imbalances, gut issues, and autoimmunity, you may have received several diagnoses from the conventional model. I’m here to tell you that there may be one common thread to your seemingly unrelated symptoms.

My training in functional medicine has taught me that our bodies are completely interconnected, and more surprisingly, these different body systems (endocrine, gastrointestinal, and immune system) are always communicating with one another.

If you are dealing with multiple diagnoses, I encourage you to work with a practitioner that specializes in a functional medicine approach. You may require in-depth functional laboratory testing to assess your gut microbiome and sex and adrenal hormones.

While these tests are an investment, the results are powerful. With these results in hand, your practitioner can help you decode your symptoms from a whole body systems perspective, and offer you a comprehensive diet, supplement, and lifestyle program that can help you finally put your symptoms into remission.

Resources:

1. Mcgregor BA, Murphy KM, Albano DL, Ceballos RM. Stress, cortisol, and B lymphocytes: a novel approach to understanding academic stress and immune function. Stress. 2016;19(2):185-91.
2. Montesinos MDM, Pellizas CG. Thyroid Hormone Action on Innate Immunity. Front Endocrinol. 2019;10:350.
3. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-38.
4. Mobeen H, Afzal N, Kashif M. Polycystic Ovary Syndrome May Be an Autoimmune Disorder. Scientifica. 2016;2016:4071735.
5. Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017;4:14.
6. Mu Q, Kirby J, Reilly CM, Luo XM. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017;8:598.
7. Ghosh SS, Wang J, Yannie PJ, Ghosh S. Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development. J Endocr Soc. 2020;4(2):bvz039.
8. Luu M, Visekruna A. Short-chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells. Eur J Immunol. 2019;49(6):842-848.

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