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Leaky Gut: A Contributor to Autoimmune Condition Onset

Autoimmunity is a mysterious creature. So many highly variable conditions fall under its umbrella. In autoimmunity, the immune system’s white blood cells cannot tell the difference between healthy body tissues and harmful antigens and end up attacking and eventually destroying the tissues and organs being attacked.  It’s no wonder it has taken so long to figure out that all of the nearly 100 known autoimmune diseases have the same root causes.

Who would have ever thought early on, that diseases like type 1 diabetes, Graves’ disease, lupus, scleroderma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, Sjogren’s, celiac disease, connective tissue disease, chronic fatigue syndrome and so many more, could all be so tightly linked?

Nearly 24 million Americans suffer from an autoimmune condition, yet as Donna Jackson Nakazawa points out in her book, The Autoimmune Epidemic, awareness around autoimmune diseases is lacking. Most people, she notes, cannot name even one autoimmune condition when asked.

The National Institutes of Health estimates that in comparison to the 24 million Americans with autoimmune diseases, only about 9 million have cancer and 16 million have coronary disease. Autoimmunity affects a large number of women, and it tends to strike in their prime (aka, the child-bearing years). About 9.8 million women are afflicted with autoimmunity, versus the 2.2 million women living with breast cancer, yet how many major league sports players are wearing, say, neon green shoes and jerseys in support of autoimmune disease awareness and research (1)?

What are some possible causes of autoimmune diseases?

What makes an individual susceptible to such unauthorized self-attacks is somewhat murky, but research is certainly closing in, now that there is an understanding that no matter what organ system is involved,  all autoimmune conditions have the same basic underlying root causes.  In his 2012 paper on Autoimmunity and Leaky Gut, Alessio Fasano, M.D., of the University of Maryland School of Medicine, proposes that autoimmunity is most likely caused by genetic predisposition, a miscommunication between innate and adaptive immunity, exposure to environmental triggers and loss of intestinal barrier function, or increased intestinal permeability, which is also known as Leaky Gut Syndrome (2).

What is leaky gut?

Leaky Gut Syndrome is the disruption of intestinal tight junctions, which typically only allow very small molecules to pass through the lining of the GI tract and into the blood stream. The disruption of the tight junctions allows large molecules to pass through the intestinal barrier and into the blood stream. These large molecules can include some bacteria and their toxins, undigested proteins, fats and wastes that are not normally allowed to pass through. When these antigens “leak” through the intestine and into the blood stream, they are then tagged by the immune system as non-self.

Antibodies are made for these non-self-labeled antigens, and when later exposures occur, the immune system mounts an inflammatory response, which targets the body’s own tissues and organ systems. This is how delayed food hypersensitivities, which are food allergies (via non-IgE-mediated immune pathways), that develop and cause inflammatory symptoms and even autoimmunity. The onset of autoimmunity can occur much later than when intestinal permeability is first compromised.

What research indicates leaky gut is a factor in the onset of an autoimmune condition?

Type 1 diabetes is a prime example. Gastrointestinal symptoms in type 1 diabetes are often attributed to autonomic neuropathy, which is said to slow down GI transit time (3).  However, other studies suggest that increased intestinal permeability (IIP) is the cause of both the onset of type 1 diabetes and GI symptoms frequently experienced in type 1 diabetes (4). In a study looking at intestinal permeability of diabetic prone research mice, Meddings et al., found that increased intestinal permeability preceded the onset of diabetes by at least one month (5).

Watts et al, replicated this study and found that increased intestinal permeability preceded the onset of type 1 diabetes by 2-3 weeks. Other researchers then looked further at the protein called zonulin, which is known to regulate intestinal permeability. They found that zonulin levels were increased, along with intestinal permeability, before the onset of diabetes in the same animal model. When they administered a zonulin-inhibiting drug, they were able to decrease the incidence of type 1 diabetes (6).

Human studies have shown that about 50% of people with type 1 diabetes have elevated zonulin levels and increased intestinal permeability, and that 25% of unaffected family members of the type 1 diabetics studied, also had elevated zonulin levels and increased intestinal permeability. This suggests that although elevated zonulin levels and increased intestinal permeability commonly are a part of the pathway to diabetes onset, there are still other factors involved in the development of the disease, such as genetic susceptibility (7). This somewhat complicates our understanding of the role that leaky gut plays in the development of autoimmune conditions. It seems that for autoimmunity of any kind to set up, the conditions need to be “just right”, with all of the necessary elements presenting themselves. Although we know leaky gut definitely does play a significant role for a good many people with autoimmune conditions, it remains difficult to predict and prevent these autoimmune conditions because of other factors which are clearly at play, but not fully understood.

How would I know if I had leaky gut or if I am at risk for developing it?

Leaky gut seems to be sometimes caused by environmental antigens in the first place, and other times affected and perpetuated by environmental antigens. Exposure to gliadin, the primary environmental/food trigger of autoimmunity in celiac disease, seems to be the necessary factor to increase zonulin levels and therefore, intestinal permeability, which leads to the autoimmune response in these patients.

Interestingly, several animal and human studies have linked gliadin to the autoimmune response in type 1 diabetes (8, 9, 10). Fasano et al, more recently studied and showed a connection between elevated levels of antibodies to Glo3 (wheat-related protein), zonulin and pancreatic islet cell autoimmunity in kids with type 1 diabetes (11).

What’s more, they also found that levels Glo3 antibody levels corresponded to breastfeeding duration, meaning that antibody levels were lower with longer breastfeeding duration. Glo3 antibodies were also directly linked to the level of exposure to gliadin/gluten-containing foods in kids with islet cell autoimmunity, but not in kids who did not have islet autoimmunity (the controls). These findings suggest that there is a difference in the immune response of the GI tract lining between the children with islet autoimmunity and those without. It is interesting that breastfeeding duration is a factor. Since a great deal of research suggests that the bacteria which inhabit the GI system impact the GI immune response, it may be reasonable to hypothesize that this is how breastfeeding, which is a means of inoculating infants’ GI tracts with friendly bacteria, may help promote an appropriate and safe response to potential environmental and food antigen exposures. Recently it was proposed that the bacteria of the GI tract do regulate the function of the intestinal barrier, including the extent of intestinal permeability (12).

How can I try to prevent onset of leaky gut in my baby if I have an autoimmune condition?

Prevention of autoimmunity and related conditions in children may be promoted with longer durations of breastfeeding, such as exclusively for the first 6 months of life and continuing on until one to two years of age, which supports a healthy GI flora, or population of friendly bacteria.  Including cultured foods in the diet and supplementing with probiotics can help keep the GI flora intact as well.

How is leaky gut treated?

If a stool or urine test show dysbiosis (when normal and healthy levels of intestinal bacteria are altered; i.e., an overgrowth of harmful bacteria), this indication has been linked to an increase in intestinal permeability as well as the increase in recent years of not only autoimmunity, but obesity, allergy and inflammatory and functional bowel disorders, like irritable bowel syndrome and inflammatory bowel disease (both IBS and IBD are autoimmune-related conditions).

Based on research findings, it is worthwhile for anyone with any of these conditions to work with a qualified health professional who can design gut-healing program to treat dysbiosis and promote gut health restoration, which follows the “5 R” Approach of Functional Medicine:

  • “Remove” pathogens and allergens.
  •  “Replace” digestive secretions.
  • “Reinoculate” the GI tract with condition-specific beneficial bacteria.
  •  “Repair” the lining of the GI tract with special gut-healing nutrients.
  •  “Rebalance” with lifestyle choices which promote a healthy GI tract and function (i.e., adequate sleep and exercise, etc.).

Physicians and Registered Dietitians trained in functional medicine are often open to and knowledgeable about nutritional and herbal supplements. If you are interested in these kinds of complimentary therapies, finding a practitioner(s) who is trained in functional medicine can be very worthwhile.

Questions for your doctor:

  • Will you run the test to determine whether I have leaky gut and a gliadin sensitivity?
  • If you do not wish to run the tests, will you partner with a functional medicine health provider who will?

1)     Nakazawa, Donna Jackson. New York : Simon & Schuster, c2008.
2)     Fasano A (2012) Clinic Rev Allerg Immunol (2012) 42:71–78
3)     Fasano A (2008) Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol 173:1243–1252.
4)     Carratù R, Secondulfo M, de Magistris L et al (1999) Altered intestinal permeability to mannitol in diabetes mellitus type I. J Pediatr Gastroenterol Nutr 28:264–271.
5)     Meddings JB, Jarand J, Urbanski SJ et al (1999) Increased gastrointestinal permeability is an early lesion in the spontaneouslydiabetic BB rat. Am J Physiol 276:G951–G957.
6)     Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A (2005) Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A 102:2916–2921.
7)     Sapone A, de Magistris L, Pietzak M et al (2006) Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55:1443–1449.
8)     Scott FW, Cloutier HE, Kleeman R et al (1997) Potential mechanisms by which certain foods promote or inhibit the development of spontaneous diabetes in BB rats. Dose, timing, early effect on islet area, and switch in infiltrate from Th1 to Th2 cells. Diabetes 46:589–598.
9)     Visser J, Rozing J, Sapone A, Lammers K, Fasano A (2009) Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N YAcad Sci 1165:195–205.
10)  Visser JT, Lammers K, Hoogendijk A et al (2010) Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetesprone BioBreeding rat. Diabetologia 53:2621–2628
11)  Simpson M, Mojibian M, Barriga K, Scott F, Fasano A, Rewers M, Norris J (2009) An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitus. Pediatr Diabetes 10:563–572.
12)  Hooper LV, Gordon JI. Commensal host–bacterial relationships in the gut. Science 2001;292:1115–8.


About the Author
Angie King-Nosseir MS, RD is an Integrative and Functional Registered Dietitian, with a passion for walking with people along their path toward health transformation. Angie has a Master’s degree in Nutrition, is a Certified LEAP Therapist, corporate wellness health coach, freelance nutrition and wellness writer, and certified yoga instructor. She is trained in Functional Nutrition and Medicine through the Institute for Functional Medicine and in Food as Medicine through the Center for Mind-Body Medicine.

This blog post was originally published by, written by Angie King-Nosseir MS, RD, and first published on Dec 18, 2012.

This post contains the opinions of the author. Autoimmune Association is not a medical practice and does not provide medical advice, diagnosis, or treatment. It is your responsibility to seek diagnosis, treatment, and advice from qualified providers based on your condition and particular circumstances. Autoimmune Association does not endorse nor recommend any products, practices, treatment methods, tests, physicians, service providers, procedures, clinical trials, opinions or information available on this website. Your use of the website is subject to our Privacy Policy.

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