In today’s functional medicine practice, practitioners like myself are confronted with a myriad of chronic inflammatory conditions and autoimmune diseases. Functional medicine is often referred to as "systems medicine" as it understands the importance of assessing and treating all systems individually, while also keeping the interconnectedness of these systems in mind. When dealing with autoimmunity, however, one system in particular, the gastrointestinal system, seems to have more and more clinical relevance with autoimmunity, especially with a condition called leaky gut.
What is leaky gut?
Leaky gut (also called increased intestinal permeability) refers to a condition where the intestine is more permeable than normal, meaning that materials can cross in and out of the intestine more than they should. A dangerous result of this scenario can be increased inflammation, immune dysregulation, and ultimately the onset of autoimmunity. Leaky gut itself is not a specific diagnosis, and the concept is still relatively controversial in today’s mainstream medicine model.
What are the symptoms associated with leaky gut?
Patients who suffer from leaky gut syndrome can experience a variety of gastrointestinal symptoms such as stomach pain, cramps, gas, diarrhea, and bloating.10 They are also often more sensitive to certain foods13 and more likely to experience migraines.24 However, clinical studies demonstrate that a large number of patients with leaky gut can display “seemingly unrelated” symptoms such as eczema and psoriasis, brain fog and depression, anxiety and insomnia, various aches and pains, and generalized inflammation.
What causes leaky gut?
How leaky gut occurs is not entirely understood. A healthy gut is naturally permeable through tight junctions that allow very small molecules to enter the bloodstream. The amount of permeability is predominantly regulated by a protein called zonulin, which acts like a gatekeeper for the tight junctions. Our current understanding is that increased intestinal permeability seems to be the result of a malfunctioning of these tight junctions15 through the overexpression of zonulin. There is growing evidence that chronic stress, extended NSAID use, food sensitivities, gluten intolerance, and the presence of pathogenic bacteria, yeasts, viruses, toxins, and inflammation may be common causes driving this mechanism. The leakage of these substances into the bloodstream can further lead to immune upregulation and may be a cause for developing autoimmune disease.6,8
It is important to note that even though many practitioners claim that leaky gut causes autoimmune diseases, it may be the case that the diseases, instead, cause leaky gut. Studies have shown that patients suffering from autoimmune diseases commonly exhibit an overexpression of an enterotoxin called zonula occludens zonulin. This enterotoxin increases gut permeability by reversibly opening tight junctions and hence causes leaky gut.23 Autoimmune patients frequently need to manage their condition for life, as only implementing dietary and lifestyle modifications may not be adequate for successful treatment.
Clinical experience and growing research confirms that gastrointestinal health is a cornerstone in our overall health and well-being. Since the intestinal epithelium provides a barrier between the external environment and the body, its functioning is critical for our health. The intestinal epithelium is the largest mucosal surface in the body and coordinates a number of critical functions, including digestion, absorption, and motility.7 It also significantly impacts our neuroendocrine and immune systems. Furthermore, the role of a healthy microbiome contributing to our overall health is becoming more widely accepted in mainstream science.
Thus, it is not particularly surprising that compromised intestinal permeability is a factor in several diseases, including many autoimmune conditions. Diseases that are characterized by enhanced intestinal permeability include: celiac disease, type I diabetes, multiple sclerosis and rheumatoid arthritis.4,16,17,26,28 Other conditions that are likely associated with this condition are Crohn’s disease, ulcerative colitis, eczema, ankylosing spondylitis, Reiter’s syndrome, and several other chronic inflammatory and allergic disorders.
How do I know if I have leaky gut?
If you suspect that you may have a leaky gut, a health practitioner specializing in functional medicine can help verify by testing for altered intestinal permeability.
A conventional method for assessing intestinal permeability employs two non-metabolized sugar molecules to determine if these molecules can penetrate the intestinal mucosa. The patient ingests these molecules, *lactulose* and *mannitol*, by drinking a pre-measured formula. Later, a urine sample from the patient is used to identify the degree of permeability of the intestine.2,20 This testing measures structural compromise that is seen with very advanced stages of intestinal barrier compromise. This test may or may not be adequate for assessing earlier stages of the condition.
A more recently developed test by Cyrex Laboratories, the Array 2 panel, provides a way to measure an immune response that would occur with the leaky gut syndrome. 1 Specifically, the Cyrex array panel investigates responses of antibodies to lipopolysaccharides (the bacterial endotoxins), actomyosin (the epithelial cell cytoskeleton), and zonulin and occludin (the tight-junction proteins). This testing is relatively new and not yet commonly accepted in mainstream medicine. However, this test panel may become invaluable towards detecting early on an immunological mechanism, which is often seen with leaky gut and autoimmune conditions.
How do I heal leaky gut?
In my practice, I use a variety of approaches to treat leaky gut. One of the most important steps when dealing with this condition is to change one’s diet. A recent study published in Gastroenterology demonstrated that certain foods do lead to gaps in the lining of the stomach.9 One of the most common recommendations is strict gluten avoidance, which will often result in improving symptoms associated with leaky gut and/or most autoimmune conditions.18 However, for most individuals suffering from autoimmune conditions, they often need a more comprehensive dietary approach. These patients will usually benefit from additionally avoiding foods in their diet such as dairy, soy, nightshades, nuts and seeds, and all grains and sugar. Thus, paleo diets, specific carbohydrate diets, or those diets restricting certain types of carbohydrates such as FODMAP may greatly improve leaky gut symptoms.
Next to modifying one's diet, taking a certain number of nutritional supplements have demonstrated high effectiveness in treating leaky gut. L-glutamine can help build strength in the lining of the small intestine and thereby minimizing leakage. In addition, curcumin and omega-3 fatty acids and their anti-inflammatory properties can aid in reducing both inflammation and oxidative stress that occur when tight junctions in the gut are open.19 Zinc supplements have been shown to improve gut permeability abnormalities in patients with Chrohn’s disease.5,22 Quercetin is a natural mast cell stabilizer that aids in decreasing histmine release and aids in further decreasing inflammation. Vitamin A and D are helpful for improving the mucosal immune system and the yeast Saccharomyces Boulardii has been shown to increase secretory IgA function. Although there is no "one-size-fits-all" solution to leaky gut symptoms, there are a number of valuable resources that can alleviate patients suffering from this condition.
If you suspect you may be suffering from leaky gut or have been diagnosed with an autoimmune condition, I recommend that you work with a qualified functional medicine practitioner. To learn more about how to heal leaky gut and how to prevent and treat the condition through dietary intervention, read more about our functional medicine service.
- Cyrex. Retrieved from: https://http://www.cyrexlabs.com/.
- Dastych, M., Dastych, M., Jr., Novotna, H., & Cihalova, J. (2008). Lactulose/mannitol test and specificity, sensitivity, and area under curve of intestinal permeability parameters in patients with liver cirrhosis and Crohn's disease. Dig Dis Sci, 53(10), 2789-2792. doi: 10.1007/s10620-007-0184-8.
- de Kort, S., Keszthelyi, D., & Masclee, A. A. (2011). Leaky gut and diabetes mellitus: what is the link? Obes Rev, 12(6), 449-458. doi: 10.1111/j.1467-789X.2010.00845.x
- Edwards, C. J. (2008). Commensal gut bacteria and the etiopathogenesis of rheumatoid arthritis. J Rheumatol, 35(8), 1477-14797.
- El-Tawil, A. M. (2012). Zinc supplementation tightens leaky gut in Crohn's disease. Inflamm Bowel Dis, 18(2), E399. doi: 10.1002/ibd.21926.
- Fasano, A. (2001). Intestinal zonulin: open sesame! Gut, 49(2), 159-162.
- Fasano, A. (2012). Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol, 42(1), 71-78. doi: 10.1007/s12016-011-8291-x.
- Fasano, A., & Shea-Donohue, T. (2005). Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol, 2(9), 416-422. doi: 10.1038/ncpgasthep0259.
- Fritscher-Ravens, A., Schuppan, D., Ellrichmann, M., Schoch, S., Rocken, C., Brasch, J., . . . Milla, P. J. (2014). Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology, 147(5), 1012-1020 e1014. doi: 10.1053/j.gastro.2014.07.046.
- Gecse, K., Roka, R., Sera, T., Rosztoczy, A., Annahazi, A., Izbeki, F., . . . Wittmann, T. (2012). Leaky gut in patients with diarrhea-predominant irritable bowel syndrome and inactive ulcerative colitis. Digestion, 85(1), 40-46. doi: 10.1159/000333083.
- Hollander, D. (1999). Intestinal permeability, leaky gut, and intestinal disorders. Curr Gastroenterol Rep, 1(5), 410-416.
- Hollander, D. (2002). Crohn's disease, TNF-alpha, and the leaky gut. The chicken or the egg? Am J Gastroenterol, 97(8), 1867-1868. doi: 10.1111/j.1572-0241.2002.05895.x.
- Karakula-Juchnowicz, H., Szachta, P., Opolska, A., Morylowska-Topolska, J., Galecka, M., Juchnowicz, D., . . . Lasik, Z. (2014). The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders. Nutr Neurosci. doi: 10.1179/1476830514y.0000000158.
- Konkel L., Danska J., Mazmanian S., & Chadwick L. The environment within: exploring the role of the gut microbiome in health and disease. Environ Health Perspect, 2013;121(9):a276-a281.
- Liu, Z., Li, N., & Neu, J. (2005). Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr, 94(4), 386-393.
- Makela, M., Vaarala, O., Hermann, R., Salminen, K., Vahlberg, T., Veijola, R., . . . Ilonen, J. (2006). Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin. J Autoimmun, 27(1), 54-61. doi: 10.1016/j.jaut.2006.04.003.
- Mojibian, M., Chakir, H., Lefebvre, D. E., Crookshank, J. A., Sonier, B., Keely, E., & Scott, F. W. (2009). Diabetes-specific HLA-DR-restricted proinflammatory T-cell response to wheat polypeptides in tissue transglutaminase antibody-negative patients with type 1 diabetes. Diabetes, 58(8), 1789-1796. doi: 10.2337/db08-1579.
- Navarro, F., Pearson, D. A., Fatheree, N., Mansour, R., Hashmi, S. S., & Rhoads, J. M. (2015). Are 'leaky gut' and behavior associated with gluten and dairy containing diet in children with autism spectrum disorders? Nutr Neurosci, 18(4), 177-185. doi: 10.1179/1476830514y.0000000110.
- Rapin, J. R., & Wiernsperger, N. (2010). Possible links between intestinal permeability and food processing: A potential therapeutic niche for glutamine. Clinics (Sao Paulo), 65(6), 635-643. doi: 10.1590/s1807-59322010000600012.
- Resnick, R. H. (1996). Lactulose leaves the leaky gut. Inflamm Bowel Dis, 2(3), 223-224.
- Shreiner A. B., Kao J. Y., Young V. B. The gut microbiome in health and in disease. Curr Opin Gastroenterol, 2015 Jan;31(1):69-75. doi: 10.1097/MOG.0000000000000139.
- Sturniolo, G. C., Di Leo, V., Ferronato, A., D'Odorico, A., & D'Inca, R. (2001). Zinc supplementation tightens "leaky gut" in Crohn's disease. Inflamm Bowel Dis, 7(2), 94-98.
- Tripathi, A., Lammers, K. M., Goldblum, S., Shea-Donohue, T., Netzel-Arnett, S., Buzza, M. S., . . . Fasano, A. (2009). Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A, 106(39), 16799-16804. doi: 10.1073/pnas.0906773106.
- van Hemert, S., Breedveld, A. C., Rovers, J. M., Vermeiden, J. P., Witteman, B. J., Smits, M. G., & de Roos, N. M. (2014). Migraine associated with gastrointestinal disorders: review of the literature and clinical implications. Front Neurol, 5, 241. doi: 10.3389/fneur.2014.00241.
- Vojdani, A., & Perlmutter, D. (2013). Differentiation between Celiac Disease, Nonceliac Gluten Sensitivity, and Their Overlapping with Crohn's Disease: A Case Series. Case Reports Immunol, 2013, 248482. doi: 10.1155/2013/248482.
- Westall, F. C. (2007). Abnormal hormonal control of gut hydrolytic enzymes causes autoimmune attack on the CNS by production of immune-mimic and adjuvant molecules: A comprehensive explanation for the induction of multiple sclerosis. Med Hypotheses, 68(2), 364-369. doi: 10.1016/j.mehy.2006.06.051.
- White, J. F. (2003). Intestinal pathophysiology in autism. Exp Biol Med (Maywood), 228(6), 639-649.
- Yokote, H., Miyake, S., Croxford, J. L., Oki, S., Mizusawa, H., & Yamamura, T. (2008). NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora. Am J Pathol, 173(6), 1714-1723. doi: 10.2353/ajpath.2008.080622.
- Yu, Q. H., & Yang, Q. (2009). Diversity of tight junctions (TJs) between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier. Cell Biol Int, 33(1), 78-82. doi: 10.1016/j.cellbi.2008.09.007.