Intestinal Permeability: Leaky Gut’s Role In Autoimmune Disease

Chronic diseases are becoming more and more prevalent. Millions within the United States are dealing with chronic diseases. According to Cordain, et al, more than 64 million are dealing with cardiovascular diseases, 11 million have type 2 diabetes, and cancer is the second leading cause of death in America. (1) Among these, autoimmune diseases are on the rise.  It is estimated that 14-22 million people in the US have an autoimmune disease. Some of the leading researchers, Fasano and Donohue, state, “Autoimmune diseases “are the third most common category of diseases in the US after cancer and heart disease. (2) And according to others, we have greatly underestimated the prevalence of these diseases. (3) The AARDA estimates that more than 50 million Americans have autoimmune diseases. (4) They are also among the leading causes of death in young and middle-aged women. (5) It has been stated that the majority of miscarriages are caused by these diseases. Autoimmune thyroid disease or Hashimoto’s is becoming increasingly prevalent.

Autoimmune diseases are a category of illnesses in which the immune system starts to target one’s own body. Cooper and Stroehla stated, “Autoimmune diseases as a group represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations…. The commonality between them, however, is the damage to tissues and organs that arises from response to self-antigens.” (5) One difficult part about autoimmune disease is that they can attack just about anywhere in the body. There are at least 15 diseases with a direct link and possibly over 80 that have not been connected yet. (2)

Most people with autoimmune diseases are treated with immune-suppressing and symptom-relieving medications. Cooper, Bynum, and Somers state, “Autoimmune diseases have conventionally been considered as distinct disorders, likely as a consequence of their being treated by separate medical specialties based on organ system of involvement.” For example, if you have Hashimoto’s thyroiditis you may see an endocrinologist and rheumatologist. But typically other than monitoring hormone levels most people receive the medications I described above. (3) However, there is a changing view and approach.

The cause of autoimmune diseases remains contested. Many physicians say the cause is idiopathic or unknown. However, there is a growing body of physicians and researchers looking to the gut as a primary role in these diseases and this is what I find in my practice as well. It is well known that the intestinal barrier functions to protect us from pathogens and other harmful substances, but in regards to autoimmunity this function has been compromised. Dr. Alessio Fasano is a major researcher in this area. Through his research we have begun to see what is really going on in the gut.

Fasano and Donohue theorize, “autoimmune diseases can therefore now be described by three key points. First, autoimmune diseases involve a miscommunication between innate and adaptive immunity. Second, molecular mimicry or bystander effects alone might not explain entirely the complex events involved in the pathogenesis of autoimmune diseases. Rather, the continuous stimulation by nonself-antigens (environmental triggers) seems to be necessary to perpetuate the process. Contrary to general belief, this concept implies that the autoimmune response can theoretically be stopped and perhaps reversed if the interplay between genes predisposing individuals to the development of autoimmunity and environmental triggers is prevented or eliminated. Third, in addition to genetic predisposition and exposure to triggering nonself-antigens, the loss of the protective function of mucosal barriers that interact with the environment (mainly the gastrointestinal and lung mucosa) is necessary for autoimmunity to develop.” (2) Essentially, genetic predisposition, environmental factors, and breakdown of the intestinal barrier (leaky gut) leads to autoimmunity. Two of these we can control. We can control what we are exposed to (environmental factors) and promote good gut health.

Leaky gut is being viewed by more and more as the underlying cause to many diseases in addition to autoimmunity. The blood brain barrier is also investigated along with leaky gut due to its similarity and correlation with disease. According to Daneman and Rescigno, “A correlation between children with autistic spectrum disorders and anxiety, allergy, or food intolerance has been observed. Because mast cells can mediate allergic disorders and respond to stress, it was suggested that mast cells may mediate neuroinflammation and increased BBB [blood brain barrier] permeability.” (6) This could explain the enormous increase in the rates of autism.

The intestines are complicated network to understand and loads of research is being done to understand it more. Especially with the rise of the human microbiome. We have trillions of microorganisms that live within us. They are supposed to be there, so don’t freak out. A lot of research is being poured into their symbiotic role with us and what happens when there is an imbalance. We do know the microbiota help with digestion. Furthermore, the intestines have the largest epithelial surface area in the human body. The surface area of the your gut would cover an entire tennis court. This, of course, aids in digestion. The more area, the more nutrients can be digested and absorbed. (7) But it gets much more complicated and interesting.

From what we know, the gut functions and protects us on a microscopic level. Groschwitz and Hogan explain, “Firstly, it acts as a barrier to prevent the passage of harmful intraluminal entities including foreign antigens, microorganisms and their toxins. Its second function is to act as a selective filter allowing the translocation of essential dietary nutrients, electrolytes and water from the intestinal lumen in the circulation. The intestinal epithelium mediates selective permeability via two major routes: transepithelial/transcellular and paracellular pathways. Transcellular permeability is generally associated with solute transport through the epithelial cells and predominantly regulated by selective transporters for amino acids, electrolytes, short chain fatty acids and sugars. Paracellular permeability is associated with transport in the space between epithelial cells, and is regulated by intercellular complexes localized at the apical-lateral membrane junction and along the lateral membrane. Contact between intestinal epithelial cells includes three components that can be identified at the ultrastructural level: desmosomes, adherens junctions (AJs) and tight junctions (TJs). The adhesive junctional complexes consist of transmembrane proteins that link adjacent cells to the actin cytoskeleton via cytoplasmic scaffolding proteins. The AJs and desmosomes are thought to be more important in the mechanical linkage of adjacent cells. The TJs, on the other hand, are the apical-most junctional complex and responsible for sealing the intercellular space and regulating selective paracellular ionic solute transport. The AJ and TJ complexes are also important in the regulation of cellular proliferation, polarization and differentiation.” (8)  The TJs are not static in function. They serve very important roles. TJs are “in a dynamic balance, regulated both from intracellular and extracellular events.” (9) Fasano states, “A century ago, TJs were conceptualized as a secreted extracellular cement forming an absolute and unregulated barrier within the paracellular space. The contribution of the paracellular pathway of the GI tract to the general economy of molecule trafficking between environment and host, therefore, was judged to be negligible. It is now apparent that TJs are extremely dynamic structures involved in several key functions of the intestinal epithelium both under physiological and pathological circumstances.” (10) He further states, “To meet the diverse physiological challenges to which the intestinal epithelial barrier is subjected, TJs must be capable of rapid and coordinated responses. This requires the presence of a complex regulatory system that orchestrates the state of assembly of the TJ multiprotein network.” (10)

Several proteins have been identified among tight junctions. They include occludin, claudins, junctional adhesion molecules (JAMs), and cytoplasmic plaque proteins. Occludin participates in “maintaining the intramembrane diffusion barrier.” Claudins help “determine the barrier properties of the paracellular pathway because they can completely tighten the intercellular space to solutes, and they can form paracellular ion pores.” (10) The primary purpose of these proteins is to not let anything through the barrier that can harm the body. In addition to these, the gut has the largest part of the immune system also known as gut-associated lymphoid tissue (GALT). It serves “as a containment system that prevents potentially harmful intestinal antigens from reaching the systemic circulation, and induces systemic tolerance against luminal antigens by a process that involves polymeric IgA secretion and induction of T-regulatory-cell activity. GALT is composed of immune inductive sites (Peyer’s patches) and immune effector sites (intra epithelial cells and lamina propria); studies now indicate that GALT is also composed of isolated lymphoid follicles (ILF).” (10) The GALT is very important. This cannot be overstated. ABout 80% of our entire immune system resides in the gut.

Dendritic cells are involved in the GALT system. They are toll-like receptors (TLRs) which help in determining self from non-self. “TLRs play a role in normal mucosal homeostasis and are particularly important in the interaction between the mucosa and the luminal flora.” They “direct immune responses by activating signaling events leading to elevated expression of factors, such as cytokines and chemokines that recruit and regulate the immune and inflammatory cells, which then either initiate or enhance host immune responses.” (10) Dendritic cells will send up arm-like projections into the intestines to see if there are any harmful substances, kind of like a periscope. When harmful substances are found they then initiate the inflammatory response talked about above.

How does the intestinal barrier breakdown and what causes it?  Enter, zonulin. Zonulin is a protein which modulates the tight junctions of the gut. Let me put it this way. Imagine your body as a castle and the cells of your intestinal barrier as the walls of the castle. The tight junctions are gates or drawbridges. Zonulin acts on these gates, opening them to allow passage between the cells. It was found through indirect means. Fasano states, “the discovery of zonula occludens toxin (Zot), an enterotoxin expressed by Vibrio cholerae that reversibly opens TJs, has increased our understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway.” (10) The zonulin pathway “appears to be involved in several functions, including TJ regulation responsible for the movement of fluid macromolecules, and leukocytes between the bloodstream and the intestinal lumen, and vice versa. Another potential physiological role of intestinal zonulin is the protection against microorganism colonization of the proximal intestine (innate immunity).” (11) However, it is it’s inappropriate activation that is the key to the problem.

Inappropriate activation can lead to unregulated passage of many non-self antigens, foreign invaders, through the barrier. Zonulin can be triggered by a variety of things. (10) But two stick out from the others: bacteria and gluten. These two have been linked to several pathologies. Furthermore, “A fast-growing number of diseases are recognized to involve alterations in intestinal permeability related to changes in TJ competency. These comprise autoimmune diseases, including T1D, CD, multiple sclerosis, and rheumatoid arthritis, in which intestinal TJs allow the passage of antigens from the intestinal milieu, challenging the immune system to produce an immune response that can target any organ or tissue in genetically predisposed individuals.” (12)

Part of a lecture. But it illustrates what is happening well. It will start at about 38m in and it is about 1 min long.

Clinically, we found other things that disrupt the barrier. Diet, food sensitivities, pesticides, herbicides, stress, and pathogens can all disrupt the barrier. According to Groschwitz and Hogan, immune cells, alcohol, NSAIDs, and pathogens can increase leaky gut.  Cytokines such as IFNγ, IL-10, and TNFα, activity can also disrupt TJs causing leaky gut. (8) Medications like antibiotics can wreak havoc on normal flora. Which in turn leads to barrier dysfunction. Our microbiome is an essential part to our barrier, immune system, and digestion.

Needless to say, the microbiome is a hot topic today. Many scientists are trying to map the residents and compare microbiome populations with human populations. The commensal bacteria are numerous with some studies estimating the number in the trillions, more numerous than all of your cells. Tlaskalová-Hogenová, et al, states, “the majority of epithelial surfaces of our body, such as the skin and mucosa, are colonized by a vast number of microorganisms; these represent the so-called normal microflora, the microbiota. The microbiota comprises mainly bacteria; however, viruses, fungi and protozoans are also present. Our microbiota contains trillions of bacterial cells, 10 times more cells than the number of cells constituting the human body. Most of the commensal bacteria are symbiotic; however, after translocation through the mucosa or under specific conditions, such as immunodeficiency, commensal bacteria could cause pathology.” (7) Once thought to be insignificant, the microbiota actually serve a very important role. They are part of the mechanisms that protect us from pathogens. Tlaskalová-Hogenová, et al, state, “when the microbiota has an optimal composition, it prevents attachment and multiplication of pathogenic or virulent microorganisms on these surfaces and the invasion of these microorganisms into epithelial cells and the circulation. The intestinal microbiota plays an important role in pathogen resistance, both by direct interaction with pathogenic bacteria and by influencing the immune system.” (7) When the microbiota are invaded by pathogens or disrupted via some outside means such as antibiotics or pesticides, their function breaks down. This is called dysbiosis. Dysbiosis can create an environment very prone leaky gut. As illustrated earlier, microorganisms can activate the zonulin pathway causing disruption in the TJs making the intestines more permeable. Leaky gut allows pathogens and proteins through, which normally cannot. This in turn causes the immune system to become activated creating inflammation in the area. This inflammation can cause a variety of issues and due to biochemical individuality and genetic predisposition there are many diseases and disorders that can be caused. Thus, providing ample evidence and linking it with autoimmune diseases. The increased inflammation can be prolonged and become systemic. Due to prolonged exposure time, non-self antigens can get confused with self-antigens creating autoimmunity.

In an editorial of the Journal of Rheumatology, Edwards states that the gut microbiome, though symbiotic, are implicated in cases of rheumatoid arthritis. (14) Maynard, et al, further described the role of dysbiosis in causing many gastrointestinal complaints as well as others. “Dysbiosis is most often associated with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, and necrotizing enterocolitis in premature infants, although it is increasingly linked to a number of extraintestinal immune-mediated diseases, including rheumatoid arthritis, multiple sclerosis, diabetes, atopic dermatitis and asthma, but also obesity and metabolic syndrome, all of which could well have their pathogenic origins in untoward reactivity of the immune system to the microbiota.“ (15) Dysbiosis can be linked with persistent infections. H. pylori, Borrelia burgdorferi, and S. typhi are implicated in many persistent infections. Often these infections are chronic with few characterizing symptoms. Therefore, they can go unnoticed for years. (16) Muller, et al, describes the process in which “The immunomodulatory properties of the pathogen reprogram the immune system towards immunological tolerance and assist the bacteria in establishing persistent infection.” (17)  This further illustrates the complex nature of the intestinal barrier, microbiota, and disease.

Another aspect is the intestinal mucosal barrier has similar properties to the blood brain barrier (BBB) further complicating the issue. It is likely that when leaky gut exists so does a breakdown in the BBB. Our BBB is very important. It protects our brain from harmful substances. As we all know, we need our brain safe and functioning well. “An important point is that neither barrier functions alone, but within the context of an organism, and thus, the function of each barrier may influence the other. For instance, food molecules that pass through the GIB into the blood stream can act on the BBB, and CNS molecules that leave the brain can access the GIB.” (6)  To illustrate this point further, “from the perspective of neuroinflammation studies, chemokine research has followed a long and complex odyssey beginning with subset-specific chemoattractants, which seemed likely to mediate the cautious recruitment of leukocytes into the CNS and PNS. Along the way, chemokine receptors were discovered on neural cells, and other CNS-resident cells were shown capable of elaborating chemokine ligands.” (13) The evidence of these in the context of BBB breakdown in conjunction with the prevalent idea today of the brain being on “fire” show the relevance and importance of these barriers in these diseases. Neuroinflammation presents with a variety of symptoms including brain fog, depression, and anxiety. Thus, showing the importance of a big picture approach with these diseases especially autoimmune.

Earlier we looked at diseases linked to dysbiosis. Now, let’s look at diseases implicated with leaky gut directly. Among the autoimmune diseases being researched are inflammatory bowel disease, celiac disease, gluten ataxia, multiple sclerosis, and type I Diabetes.

Inflammatory bowel disease or IBD is among the most researched in its connection with leaky gut. Groschwitz and Hogan suggests just that in their pathogenesis of IBD. They described, “an emerging model of the pathogenesis of IBD suggests there are three essential factors: 1) a breakdown in intestinal barrier function; 2) exposure of luminal contents to immune cells in the lamina propria; and 3) an exaggerated immune response.” (8)  The cause of leaky gut is unknown most likely because it can be caused by multiple culprits depending on each person. Whatever the culprit is, it is likely to be causing the activation of the zonulin pathway as discussed earlier. Nonetheless, IBD produces many cytokines that perpetuate the cycle. “The production of cytokines, including interferon-γ and tumor necrosis factor-α, secondary to the inflammatory process serve to perpetuate the increased intestinal permeability by reorganizing TJ proteins ZO-1, JAM 1, occludin, claudin-1, and claudin-4.52,53,54,55 In this manner, a vicious cycle is created in which barrier dysfunction allows further leakage of luminal contents, thereby triggering an immune response that in turn promotes further leakiness.” (10) Unless the inflammation is controlled and the intestinal barrier healed the disease will continue to dominate. Furthermore, exacerbation of the disease can happen if careful measures are not taken to ensure an intact barrier.

Celiac disease has long been linked to leaky gut. Gliadin, a protein within gluten, has been implicated as the cause of the inflammatory condition. (18) Gluten is made up of multiple proteins gliadin being one of them. But because the proteins are so large they are unable to pass the mucosal barrier without leaky gut. Gliadin attaches itself to receptors activating the release of zonulin. Zonulin then activates the cells to open the tight junctions and allowing gluten in. Increased zonulin levels have also been shown in CD cases. (8) In rat models, leaky gut is accompanied by dysbiosis. (18) Fortunately, unlike other autoimmune diseases the direct cause is known in the case of CD. To truly heal, the patient needs to go off gluten completely. This can be tracked via blood markers. But overtime the inflammatory agents will decrease and the intestinal barrier will normalize. (19)

Sapone, et al, gave possible reasons for the increase in gluten related disorders. These include frequency of consumption and hybridization to increase gluten quantity in wheat. (20) Further, we do not process it in the same ways. Our grandparents and many around the world still soak and sprout the wheat. After which they use wild yeast for leavening. This process helps break down the gluten for consumption. In addition to this, we often harvest early. Many farmers harvest twice per year by using glyphosate, Roundup. The pesticide can dry the plant allowing for early harvest. When harvest is done traditionally, gluten has time to break down within the plant. Another factor, is glyphosate itself. It can act as antibiotic and also make you more sensitive to gluten.

Gluten has been implicated in other diseases as well not just celiac disease. (21) In fact, it is now being considered that there is a spectrum of gluten related disorders. (20) I am included in this lot. Gluten causes my migraines. For others I have seen it cause eczema or chronic fatigue syndrome. Further complicating it, Dr. Vojdani has shown that gluten can cause cross-reactivity with other foods. These other foods have similar protein structures to gluten and can cause the same immunological response. (22) This can make it difficult in figuring out the root cause and why many require an elimination diet where you go without certain inflammatory foods for 30 days and then slowly reintroduce them until you can find the one causing the problem.

Another disease directly related to gluten is gluten ataxia. According to Sapone, et al, “gluten ataxia (GA) was originally defined as otherwise idiopathic sporadic ataxia with positive serological markers for gluten sensitization. Like CD, it is an autoimmune disease characterized by damage to the cerebellum resulting in ataxia.” (20) Your cerebellum helps with balance, posture, tone, and many other things. With ataxia you lose control over your movements and coordination. Also like CD, a gluten-free diet can help halt and possibly resolve this disorder.

Multiple sclerosis, a CNS demyelinating disease, has been connected with gluten sensitivity as well. Reichelt, et al, state, “Increased levels of IgA and IgG antibodies in serum against gluten and gliadin and possibly also for casein in MS patients may indicate a possible increased gut permeability to certain proteins.” (23) This further illustrates gluten as a major culprit in intestinal permeability cases as Dr. Fasano has shown. Moreover, showing the connection with leaky gut, autoimmune diseases, and brain disorders.

Type I Diabetes (T1D) has been linked to increased permeability as well. One of the strongest links we have according to Fasano. Vaarala writes of diabetic rats having high intestinal permeability. Furthermore, the increased intestinal inflammation causing the permeability being caused by gluten.“In vitro gliadin-stimulation of small intestinal biopsies taken from patients with T1D caused increase in the numbers of T cells and their activation.” (24) Interestingly, there was a case study involving a 5-year and 10-month old boy who developed signs and symptoms of diabetes and was admitted to the hospital. Instead of administering insulin therapy, the boy was put on a gluten-free diet and observed for 20 months. His blood glucose and HbA1c levels began to decline and he never needed insulin. (25) Further illustrating the point, Visser, et al, stated that “Gliadin has recently been the object of a series of studies that aim at establishing its role in the pathogenesis of T1D. Early introduction of gliadin-containing cereals was recently reported to increase the risk of islet cell autoimmunity in humans.” (18)

Much remains unclear. If the zonulin pathway is activated, what all can activate it? Is it possible to narrow down to just one culprit and is there a different culprit in every case? Why do some people handle gluten well while others cannot? What role do genes and epigenetics have in this? Is dysbiosis a cause or an effect? Many questions remain unanswered. (8,10,15) The jury may remain out on specific causations, however, possible solutions are being investigated. In our office, we often find one major culprit in most people. This doesn’t mean that it is the only thing going in someone’s body. Neither does it mean that nothing else could arise. But for instance, the underlying cause of my migraines was gluten. However, I had to heal my intestinal barrier by eating well and promoting healthy microbiota. Other things have arose as well with my health. This leading back to the idea that eating well and moving well is the best preventative medicine and the foundation of optimal health. I am going to talk about a few of these solutions in more detail.

One avenue is to use probiotics to influence and support the commensal bacteria. In their article, Delcenserie, et al, state, “the intestinal microbiota acts as primary agent in the development of the postnatal immune system such as oral tolerance and immunity. The interaction of probiotics and enterocytes is key to the initiation of immunomodulation. Probiotics act on a wide variety of cells in the intestine to modulate the immune system towards a pro or anti-inflammatory action, depending on strain, setting and immunological parameters measured, and the type of cells being acted upon.” (26)  However, dysbiosis might not be an issue in all cases. Therefore, it may not provide any relief to some patients. Further, what type of probiotic should be considered. There are many on the market. On top of that each patient must be taken individually. What works for one patient might not and often does not work for another. That is why I typically do not give probiotics to my patients but rather recommend that they consume probiotic foods. What is the difference? Probiotic capsules contain a certain amount of bacteria. We have trillions of different kinds within us. So it is hard to say which microbes you need. And often I find probiotics to cover the symptoms rather than getting at the root cause. Many who stop taking the probiotics have their symptoms return. I recommend probiotic foods such as grass-fed yogurt, fermented pickles, sauerkraut, kimchi, and eating lots of organic, locally grown vegetables and fruits. Lightly rinse the fruit and veggies there is a good deal of probiotics with them. Go for a walk in nature, enjoy playing outside. All of these combined will go a long way in helping repopulate the gut with good bacteria and microbes.

Another solution has been widely promoted by many holistic practitioners is the Paleo or ancestral diet. There are some great aspects to this but widely differing views. We simply term it the nutrient dense diet. It is going back to the way your grandparents ate and others around the world eat. Our dietary lifestyle has changed over the centuries but more especially after the industrial revolution. Where we used to eat more whole foods that we personally grew, gathered, or hunted, we now buy from markets. These foods are heavily processed and many chemicals such as preservatives are added. Furthermore, the amount of certain foods we consume has changed. We consume a lot more carbohydrates especially refined sugar. Cordain, et al, explains this well, “With the initial domestication of plants and animals, the original nutrient characteristics of these formerly wild foods changed, subtly at first but more rapidly with advancing technology after the Industrial Revolution. Furthermore, with the advent of agriculture, novel foods were introduced as staples for which the hominin genome had little evolutionary experience. More importantly, food-processing procedures were developed, particularly following the Industrial Revolution, which allowed for quantitative and qualitative food and nutrient combinations that had not previously been encountered over the course of hominin evolution.” (1) Many have praised the industry because there is more food available than ever before. However, the quality has suffered greatly. “Although dairy products, cereals, refined sugars, refined vegetable oils, and alcohol make up 72.1% of the total daily energy consumed by all people in the United States, these types of foods would have contributed little or none of the energy in the typical preagricultural hominin diet. Additionally, mixtures of foods…make up the ubiquitous processed foods (eg, cookies, cake, bakery foods, breakfast cereals, bagels, rolls, muffins, crackers, chips, snack foods, pizza, soft drinks, candy, ice cream, condiments, and salad dressings) that dominate the typical US diet.” (1) Dr. Cordain and others propose going back to a more ancestral or Paleo diet consisting of more whole foods including meat, vegetables, fruits, and unrefined fats. This diet excludes most refined foods, vegetable oils, sugar, limiting grains and sometimes dairy. Their rationale is that “evidence gleaned over the past 3 decades now indicates that virtually all so-called diseases of civilization have multifactorial dietary elements that underlie their etiology, along with other environmental agents and genetic susceptibility.” (1) We need to move back to 1 ingredient foods. The whole food diet which consists of no packaged, pre-made foods. A typically healthy plate should be divided into 25% quality protein, 25% starchy veggie, and 50% veggies and fruits of multiple colors. Grains should be limited unless you are sensitive to them. Dairy is a great nutrient-dense food if it comes from grass-fed/pasture-raised animals and you are not sensitive to it. Among with protein, organ meats and bone broth should be consumed regularly. This will go along way in helping to heal and recover from autoimmune disease.

Conclusion

Autoimmunity is becoming an increasing problem. Researchers are working frantically to find underlying causes and solutions. I have included several quotes from the top researchers in this field. With the recent developments and increased understanding of intestinal barrier function, the connection between the gut and autoimmune diseases is remarkable. As the barrier breaks down, pathogens and other non-self antigens make it through. This in turn creates an inflammatory response which can become cyclical in nature. As the inflammation becomes prolonged and the exposure to the antigens continue, the immune system starts to confuse non-self with self. This can happen in a variety of places thus explaining the numerous amount of the autoimmune diseases. The role of leaky gut and autoimmunity is still trying to be understood in greater detail. Nonetheless, the role is significant and possibly the primary cause in a host of terrible diseases. Practitioners are now utilizing this information to find solutions to help treat these complex issues. So I highly recommend finding a holistic practitioner in your area who can root out the underlying cause. This is something we treat on a daily basis. I hope this helps you understand what really is going on and provides much needed answers.