Surely, few of you have heard of intestinal permeability or Leaky Gut Symdrome. This recently discovered issue which doctors too often are not aware of, is very important in the relationship between diet and disease.

This dangerous condition could be the cause and the definitive answer to your illness where your general practitioner and the countless visits by specialists of various kinds have not been able to respond except by justifying themselves with the usual phrase: “it is the fault of stress”.


The intestine has the main task of completing the digestion of food and absorbing into the bloodstream the nutrients essential to the functioning of our body.

In addition to this well-known digestive function, the intestine also represents a very important borderline between the outside and the inside world. It is like a sort of barrier which has the task of distinguishing everything that is useful or harmless from what is dangerous.

A healthy intestine must in fact prevent pathogenic microorganisms, parasites, toxins and food antigens from entering the bloodstream in order to avoid damage [1].


The barrier function of the intestine is guaranteed by the presence of numerous defensive lines. In fact, more than two thirds of the entire immune system resides in the intestine and is equipped with a large number of lymph node stations, natural antibiotics and cells that secrete mucus able to trap pathogens that will be expelled through the stool.

In addition, the immune system closely monitors the intestinal flora, consisting of microorganisms that compete with fungi and bacteria that are pathogenic for nutrition and sites of adhesion to the intestinal mucosa.

But the most important defensive system against attacks from the outside world is represented by the intestinal mucosa or intestinal villi, numerous estroflections in the shape of fingers, very important to increase the absorbent surface of the organ, which are in turn equipped with digitiform estroflections called microvilli [1]. And it is precisely when this barrier becomes permeable or “dripping” that we are in serious trouble.

In a healthy intestine the intestinal villi are held together by the tight junctions that play a very important role in regulating the passage of substances from the intestinal lumen to the bloodstream [2,3].

The tight junctions are regulated by the intestinal microflora, by the state of inflammation and above all by food, which can compromise their integrity and consequently make them permeable [4-7].

In the 2000s, Dr. Fasano brought this problem to light by discovering that tight junctions between intestinal villi would be regulated by the levels of a protein, zonulin.

Excessive production of zonulin following sudden changes in the intestinal microflora and systemic inflammation tends to open these junctions between the intestinal villi and promote permeability [8].

The intestinal epithelium represents the largest interface (more than 2,000,000 cm2) between the external and internal environment. The appropriate regulation of intestinal junctions by modulators such as zonulin is essential for intestinal function and integrity. Tight junctions prevent the passage of potentially harmful agents such as bacteria, viruses, toxins, food allergens and macromolecules into the bloodstream [8].

In a permeable intestine, the tight junctions dilate and all these agents end up directly in the bloodstream leading to very serious consequences such as food allergies, autoimmune diseases, digestive problems and even damage to the blood-brain barrier [9].

All this, in turn, favors an increase in inflammation and the consequent hyper-production of zonulin. This triggers a vicious circle that will increasingly damage the intestinal barrier, dangerously increasing the risk of developing the complications listed above.


Permeable bowel syndrome and its high production of zonulin would be the common cause of all autoimmune diseases [8]. The basis of autoimmunity would be the concept of “molecular mimicry”, i.e. the strategy that uses external agents (viruses, bacteria, fungus, parasites but also lectins, gluten, saponins, caseins containing in some foods) to escape attacks from the host organism.

The concept is very simple: the immune system, hyper-stimulated by an inflamed permeable intestine, goes into confusion and instead of attacking the external agent (which by modifying its protein structures becomes unrecognizable as a pathogen to the host) attacks the cells of our body.

In short, understandable to all, if an external agent enters and camouflages itself by assuming “features” similar to the protein structure of cells in the islands of Langerhans in the pancreas, the immune system will attack these cells, destroying them and causing type 1 diabetes.

If an external agent enters and camouflages itself by assuming “features” similar to the cells of the central nervous system, the immune system will attack the latter, destroying them and causing multiple sclerosis. The concept of autoimmunity is brutally simple: the immune system, which should serve as protection against pathogenic microorganisms, pours itself against us by attacking and destroying us.

In the 2000s, Fasano observed that in subjects suffering from celiac disease, an autoimmune disease, the tight junctions are very open at the beginning of the disease also predisposing to other autoimmune diseases such as type 1 diabetes, Hashimoto’s thyroiditis, autoimmune hepatitis and connective tissue diseases [8].

Fasano also states that it could be assumed that the opening of the tight junctions induced by zonulin, which occurs during the initial phase of celiac disease, allows the entry of certain allergens into the intestinal submucosa, where they can trigger an autoimmune response.

In addition, Fasano observed that zonulin is also present in tissues other than the intestine and that its dysregulation could lead, in addition to autoimmune diseases and inflammation, even to malignant tumours in the affected tissues [8,10].

So far, dozens of autoimmune diseases and diseases that we know or suspect manifest themselves with the permeable bowel are. Among these we remember: allergies [11], achylosing spondylitis [12], aphthous stomatitis [13], bronchial asthma [14], autism [15], autoimmune gastritis [16], autoimmune hepatitis [17], primary sclerosing cholangitis [17], Behçet’s syndrome [18], celiac disease [19], chronic fatigue syndrome [20], Chron’s disease [21], irritable bowel syndrome [21], recto ulcerative colitis [21], depression [22], dermatitis herpetiformis [23], type 1 diabetes [24], eczema [25], childhood migraine [26], Hashimoto’s thyroiditis [27], nephropathy [28], intrahepatic pregnancy cholestasis [29], juvenile arthritis [30], lupus erythematosus [3], multiple sclerosis [32], pemphigus [33], primary biliary cirrhosis [34], psoriasis [35], rheumatoid arthritis [36], rosacea [37], schizophrenia [38], systemic sclerosis [39], miscarriage [40], urticaria [41], uveitis [42], fibromyalgia [43].

In conclusion, almost half of autoimmune diseases occur with a permeable intestine that could be the main cause or a contributing cause. In the absence of studies on the remaining autoimmune diseases we can only assume that they also have at their base a problem of high intestinal permeability.


In addition to autoimmune diseases, intestinal permeability also has important repercussions on the liver and endocrine system. Under normal conditions, the liver processes toxins and metabolic waste every day by detoxifying the body.

Under conditions of intestinal permeability, the amount of metabolic and microbial toxins entering the bloodstream increases significantly. The liver may become saturated and be unable to dispose of these toxic substances, which will then be poured into the bloodstream in bulk.

From the blood, the lymphatic system will attempt to collect and neutralize toxins, but if the liver is saturated and the lymphatic system fails to send other toxins to the liver, the body essentially becomes intoxicated [44].

Microbes grow and develop, so a condition of chronic lymphatic stasis may occur, especially in children. Persisting in this state, toxins will be forced into connective tissues, around muscles and joints, where they could cause pain known as fibromyalgia [42], or into cells, eventually creating genetic mutations (polymorphisms) and finally even cancer [10].

Moreover, the continuous state of systemic inflammation caused by increased intestinal permeability results in chronic stress for our organism [45]. In these circumstances the adrenal glands are forced to do overtime and produce the hormone cortisol (a potent natural anti-inflammatory) in larger amounts to try to extinguish the inflammation.

Overproduction of cortisol may limit the damage for a certain period of time but in the long term, continued production of this hormone will lead to collapse of the adrenal glands or “adrenal fatigue” (see the article stress and cortisol: indissoluble bond). Adrenals will no longer be able to produce cortisol and expose us dangerously to all its damage and complications (read more about it here).


The causes of intestinal permeability, as it is logical to think, lie mainly in what we ingest but also in inflammation and stress (stress causes inflammation or vice versa). Stress is not only stress from work, family and daily life but also stress induced by food. Yes, most of what we find in supermarkets is not edible to man because it is NOT species-specific food to which our body has not adapted.

When we ingest non-species-specific food, essentially inflammatory processes are created that trigger a stressful condition. If the ingestion of non-species-specific food is chronic, stress also becomes chronic. In particular, processed and refined foods such as sugar and junk food promote intestinal permeability.

The combination of high temperatures in industrial food storage, and the daily use of sugar has led researchers to study the content of advanced end products of glycation (AGE) and lipid glycates (ALE) in modern foods in order to study their possible harmfulness. Once formed, AGEs and ALEs would promote systemic inflammation, thereby increasing intestinal permeability [4]. According to this evidence, 90% of the products sold in supermarkets (highly processed foods) would be toxic to our intestines.

Alcohol is no exception and is also related to the increase in intestinal permeability [5].

The use of non-steroidal anti-inflammatory NSAIDs (such as the famous aspirin we take at the slightest hint of headache) is also associated with a high incidence of gastrointestinal disorders, and there is substantial evidence that chronic use can alter the function of the intestinal barrier and cause significant damage, including ulcers, perforations, bleeding and an exacerbation of intestinal inflammation [5].

Not only junk food, sugar and NSAIDs increase intestinal permeability and we sincerely do not even consider them the biggest problem, because in fact no one recommends them in the classic “balanced and healthy” diet.

The biggest problem is represented by all those foods that are recommended by “nutrition professionals” in any diet and that in the collective imagination are considered healthy.

What you read in the next paragraph will be very disturbing and will put a strain on your ego and the beliefs that have accompanied you for a lifetime.


Cereals, legumes and some solanaceous plants (tomatoes and potatoes) contain antinutrients, food compounds that reduce the absorption of other nutrients, mainly glycoproteins such as gliadin, lectin and saponins [46].

Recently it has been discovered that gliadin, a protein in wheat that makes up gluten [46], increases the permeability of the intestine through the production of zonulin in intestinal enterocytes [47].

In addition, gliadin, which is resistant to heat and digestive enzymes [46], is able to interact with the lymphoid tissue associated with the intestine, stimulating the immune system in celiac and non-celiac individuals and probably triggering autoimmunity conditions [48,49].

In a nutshell, cereal gluten, regardless of its genetic predisposition to celiac disease, can increase intestinal permeability and thus cause chronic systemic inflammation [47-50].

Finally, gluten is involved in several autoimmune diseases such as multiple sclerosis [51,52], type 1 diabetes [53], psoriasis [54], nephropathy and rheumatoid arthritis [46].

Gluten is not the only problem. Lectins, omnipresent proteins found in the plant kingdom, are also responsible for increased intestinal permeability [47].

In animal models, legume and cereal lectins disturb the intestinal barrier and immunological function when they bind surface glycans to intestinal epithelial cells, causing cellular disturbances and increasing intestinal permeability.

They can also facilitate the growth of negative bacterial strains, which could contribute to endotoxemia and consequently trigger low-grade chronic inflammation [55].

Saponins can increase intestinal permeability in humans and thus also endotoxemia and chronic systemic inflammation according to well known processes [56-60].

They are present in some cereals, legumes, quillaja, soya, quinoa, alpha-alpha shoots and solanaceous plants such as potatoes and green tomatoes [56-60].

Cereals and legumes, which we all think are so good and healthy, are instead ruthless killers who act silently. The problems arising from their consumption can arise even after several months or even years with serious consequences such as autoimmune diseases. Whole-grain cereals are healthier, aren’t they? There is no more incorrect statement than this! The opposite is true!

Wholegrain cereals are “better” only from the point of view of the glycemic index because they contain the skin or bran and therefore many more fibers that modulate the release of blood sugar. But it is precisely in the outer part (bran) of the cereal where the largest portion of antinutrients such as lectins and saponins is contained.

Wholegrain cereals are actually poison and devastatingly amplify the intestinal permeability [46].

Why do cereals and legumes contain these very harmful anti-nutrients? The reason is logical and lies in the mechanisms that plants have to defend themselves from predators. While animal organisms can escape or fight to defend themselves, plants are literally planted on the ground and therefore in the course of their evolution have developed their defense mechanisms: the antinutrients [46].

The clearest example to all is that of fungi or other poisonous plants. If a predator (like man) eats one of these plants, he pays the price with his death, as in the famous film “Into the Wild”. His death will be taken as an example by his fellow humans and the information that that berry or mushroom should NOT be eaten will be passed down from generation to generation. That type of plant, berry or fungus will no longer be preyed upon and consequently will proliferate to ensure the survival of its species.

Other plant organisms, however, such as fruit trees, have fruits that are appetizing but contain within them an indigestible seed. The predators, eating the fruit will distribute the seed with the stool increasing the chances of reproduction and ensuring the survival of this plant [46].

Anti-nutrients such as lectins and saponins kill parasites or small predators such as insects but are not sufficient to kill a man weighing 70 kg on average. In humans, lectins and saponins can bind to intestinal cells, destroying them and consequently increasing their permeability [56-61].


Recently a study conducted in Italy found a significant association between the consumption of handmade dairy products and increased intestinal permeability leading to irritable bowel syndrome and Chron’s disease [62].

The culprit would be a pathogen, the microbacterium Avium subsp. Paratuberculosis, capable of causing Johne’s disease, systemic infection and chronic inflammation of the intestine often associated with chronic neuritis with dysregulation of the immune system, which can affect many animals, including primates [63,64].

Researchers examining intestinal biopsy samples found the presence of this bacterium in 20 of the 23 subjects (87%) with Chron’s disease and 15 of the 20 subjects (75%) with irritable bowel syndrome [62].

Furthermore, no statistically significant association between Chron’s disease/irritable bowel syndrome and genetic predisposition, exposure to rural, urban and livestock environments was found, indicating that the development of the disease resides only in the consumption of handmade dairy products [62]. It is interesting to note that in Sardinia, where the consumption of dairy products is very high, we also have a very high prevalence of autoimmune diseases and in particular of type 1 diabetes.

In Sardinia, the incidence of type 1 diabetes in paediatric age (0-14 years) is decidedly higher than in other Italian regions, according to what emerges from the regional register, being equal to 44.8/100.000 subjects/year in the twenty-year period 1989-2009 with an annual increase of 2.12% [65,66].

Sardinia, together with Finland, has the world record for the incidence of diabetes with over 50,000 people suffering from the disease and the high consumption of dairy products is most likely one of the main causes. At the basis of this, there may once again be a problem of high intestinal permeability, as several studies suggest [24,67,68].


Intestinal permeability is a newly discovered problem, of which your doctor most likely is not yet aware, which arises through a wide range of symptoms. You may suffer from chronic fatigue, food allergies and intolerances, autoimmune diseases, digestive problems, nutritional deficiencies, skin problems, insomnia, hormonal imbalances, mood changes and presence of Candida Albicans.

Consequently, given the lack of a precise diagnostic picture, many people are affected without even knowing it and in most cases, doctors, confusing the symptoms of intestinal permeability, prescribe drugs that will not solve anything creating further damage to the intestinal barrier and beyond. However, there are tests to be done in case you doubt the health of your intestine. 

The current and most common method of diagnosing intestinal permeability is the lactulose/mannitol test. The test is simple to perform (you need to drink a sugar solution and then examine it in the urine) and allows us to assess the permeability of the intestinal wall and its functional absorption capacity by observing the levels of lactulose in the urine.

The more expensive but more reliable is the “Intestinal Antigenic Permeability Screen - Array 2” test, which measures antibodies against bacterial endotoxins (lipopolysaccharides), It identifies both transcellular and paracellular pathways of intestinal barrier penetration by large molecules with the ability to test the immune system by measuring the immune response from intestinal permeability. 

Without taking too long, these tests are valid but could be a waste of time and money. If you want to remove the scruple you can do them but in many cases it is sufficient to observe the symptoms of intestinal permeability listed above according to the scientific literature and act accordingly. 

The main strategy is to adopt an autoimmune diet protocol that provides for the removal in the trunk of cereals, legumes, dairy products, junk food, industrial products and in some cases even nuts, eggs and solanaceous plants.

In addition, some supplements have been shown to be effective against intestinal permeability.

Glutamine is currently the best supplement to combat this problem [69-76] and together with other amino acids such as arginine and leucine it seems to have even more promising effects [77-79].

Curcumin has also proven to be an excellent supplement against intestinal permeability due to its anti-inflammatory and antioxidant properties [4]. 

These strategies may not be enough. First of all, a radical change in lifestyle is needed, which should include healthy physical activity, rest, proper nutrition and dietary supplementation, and control of stressful agents.



As it was always said, health comes from the intestine and today this is scientifically proven.

A permeable intestine loses its function as a barrier between the outside world and our internal environment, exposing us to threats that can seriously compromise health such as autoimmune diseases, allergies, inflammation, poor digestion, endotoxemia, adrenal fatigue, liver complications and even malignant tumors.

The causes, as we have seen before, are manifold and could lie in daily habits that we take for granted to be healthy but are not at all. Moreover, it is interesting to note that post-agriculture foods would seem to be the major problem, confirming once again the theory of evolutionary disagreement (read article).

However, the condition of permeability of the intestine should not be taken lightly and immediate action is a must even if prevention is always the best choice. Prevention means adopting a lifestyle different from today’s, revolutionizing the habits that have always accompanied us. Prevention means choosing EVOplus.

EVOplus - Lifestyle Revolution



1. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. J Gastroenterol Hepatol. 2003;18:479–97.

2. Gonzalez-Mariscal L, Tapia R, Chamorro D. Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta. 2008;1778:729–56.

3. Laukoetter MG, Nava P, Nusrat A. Role of the intestinal barrier in inflammatory bowel disease. World J Gastroenterol. 2008;14:401–7.

4. Jean Robert Rapin and Nicolas Wiernsperger. Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine. Clinics (Sao Paulo). 2010 Jun; 65(6): 635–643.

5. Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3–20. quiz 1–2.

6. Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut. 2006;55:1512–20.

7. Edelblum KL, Turner JR. The tight junction in inflammatory disease: communication breakdown. Curr Opin Pharmacol. 2009;9:715–20.

8. Wenle Wang, Sergio Uzzau, Simeon E. Goldblum and Alessio Fasano. Human zonulin, a potential modulator of intestinal tight junctions. Journal of Cell Science 113, 4435-4440 (2000).

9. R. Lu, W. Wang, S. Uzzau, R. Vigorito, H. R. Zielke, and A. Fasano. Affinity Purification and Partial Characterization of the Zonulin/Zonula Occludens Toxin (Zot) Receptor from Human Brain. Journal of Neurochemistry Lippincott Williams & Wilkins, Inc., Philadelphia © 2000 International Society for Neurochemistry.

10. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.

11. Liu Z1, Li N, Neu J. Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr. 2005 Apr;94(4):386-93.

12. Vaile JH, Meddings JB, Yacyshyn BR, Russell AS, Maksymowych WP. Bowel permeability and CD45RO expression on circulating CD20+ B cells in patients with ankylosing spondylitis and their relatives. J Rheumatol. 1999 Jan;26(1):128-35.

13. Veloso FT, Saleiro JV. Small-bowel changes in recurrent ulceration of the mouth. Hepatogastroenterology. 1987 Feb;34(1):36-7.

14. Benard A1, Desreumeaux P, Huglo D, Hoorelbeke A, Tonnel AB, Wallaert B. Increased intestinal permeability in bronchial asthma. J Allergy Clin Immunol. 1996 Jun;97(6):1173-8.

15. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

16. Greenwood DL1, Crock P, Braye S, Davidson P, Sentry JW. Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability. Eur J Pediatr. 2008 Aug;167(8):917-25. doi: 10.1007/s00431-007-0664-z. Epub 2008 Jan 24.

17. Terjung B1, Spengler U. Atypical p-ANCA in PSC and AIH: a hint toward a “leaky gut”? Clin Rev Allergy Immunol. 2009 Feb;36(1):40-51.

18. Fresko I, Hamuryudan V, Demir M, Hizli N, Sayman H, Melikoğlu M, Tunç R, Yurdakul S, Yazici H. Intestinal permeability in Behçet’s syndrome. Ann Rheum Dis. 2001 Jan;60(1):65-6.

19. Schulzke JD1, Bentzel CJ, Schulzke I, Riecken EO, Fromm M. Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue. Pediatr Res. 1998 Apr;43(4 Pt 1):435-41.

20. Maes M, Coucke F, Leunis JC. Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome. Neuro Endocrinol Lett. 2007 Dec;28(6):739-44.

21. Caradonna L, Amati L, Magrone T, Pellegrino NM, Jirillo E, Caccavo D. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res. 2000;6(3):205-14.

22. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

23. Kieffer M, Barnetson RS. Increased gliadin antibodies in dermatitis herpetiformis and pemphigoid. Br J Dermatol. 1983 Jun;108(6):673-8.

24. Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Cartenì M, Generoso M, Iafusco D, Prisco F, Laghi F, Riegler G, Carratu R, Counts D, Fasano A. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006 May;55(5):1443-9.

25. Hamilton I, Fairris GM, Rothwell J, Cunliffe WJ, Dixon MF, Axon AT. Small intestinal permeability in dermatological disease. Q J Med. 1985 Sep;56(221):559-67.

26. Amery WK, Forget PP. The role of the gut in migraine: the oral 51-Cr EDTA test in recurrent abdominal pain. Cephalalgia. 1989 Sep;9(3):227-9.

27. Sasso FC, Carbonara O, Torella R, Mezzogiorno A, Esposito V, Demagistris L, Secondulfo M, Carratu’ R, Iafusco D, Cartenì M. Ultrastructural changes in enterocytes in subjects with Hashimoto’s thyroiditis. Gut. 2004 Dec;53(12):1878-80.

28. Rostoker G1, Wirquin V, Terzidis H, Petit-Phar M, Chaumette MT, Delchier JC, Belghiti D, Lang P, Dubert JM, Meignan M, et al. Mucosal immunity in primary glomerulonephritis. III. Study of intestinal permeability. Nephron. 1993;63(3):286-90.

29. Reyes H1, Zapata R, Hernández I, Gotteland M, Sandoval L, Jirón MI, Palma J, Almuna R, Silva JJ. Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy? Hepatology. 2006 Apr;43(4):715-22.

30. Picco P, Gattorno M, Marchese N, Vignola S, Sormani MP, Barabino A, Buoncompagni A. Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters. Clin Exp Rheumatol. 2000 Nov-Dec;18(6):773-8.

31. Apperloo-Renkema HZ, Bootsma H, Mulder BI, Kallenberg CG, van der Waaij D. Host-microflora interaction in systemic lupus erythematosus (SLE): colonization resistance of the indigenous bacteria of the intestinal tract. Epidemiol Infect. 1994 Apr;112(2):367-73.

32. Yacyshyn B1, Meddings J, Sadowski D, Bowen-Yacyshyn MB. Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci. 1996 Dec;41(12):2493-8.

33. Kieffer M, Barnetson RS. Increased gliadin antibodies in dermatitis herpetiformis and pemphigoid. Br J Dermatol. 1983 Jun;108(6):673-8.

34. Di Leo V, Venturi C, Baragiotta A, Martines D, Floreani A. Gastroduodenal and intestinal permeability in primary biliary cirrhosis. Eur J Gastroenterol Hepatol. 2003 Sep;15(9):967-73.

35. Hamilton I, Fairris GM, Rothwell J, Cunliffe WJ, Dixon MF, Axon AT. Small intestinal permeability in dermatological disease. Q J Med. 1985 Sep;56(221):559-67.

36. Smith MD, Gibson RA, Brooks PM. Abnormal bowel permeability in ankylosing spondylitis and rheumatoid arthritis. J Rheumatol. 1985 Apr;12(2):299-305.

37. Kendall SN. Remission of rosacea induced by reduction of gut transit time. Clin Exp Dermatol. 2004 May;29(3):297-9.

38. Wood NC, Hamilton I, Axon AT, Khan SA, Quirke P, Mindham RH, McGuigan K, Prison HM. Abnormal intestinal permeability. An aetiological factor in chronic psychiatric disorders? Br J Psychiatry. 1987 Jun;150:853-6.

39. Caserta L, de Magistris L, Secondulfo M, Caravelli G, Riegler G, Cuomo G, D’Angelo S, Naclerio C, Valentini G, Carratù R. Assessment of intestinal permeability and orocecal transit time in patients with systemic sclerosis: analysis of relationships with epidemiologic and clinical parameters. Rheumatol Int. 2003 Sep;23(5):226-30. Epub 2003 Feb 15.

40. Friebe A, Arck P. Causes for spontaneous abortion: what the bugs ‘gut’ to do with it? Int J Biochem Cell Biol. 2008;40(11):2348-52. doi: 10.1016/j.biocel.2008.04.019. Epub 2008 May 18.

41. Buhner S, Reese I, Kuehl F, Lochs H, Zuberbier T. Pseudoallergic reactions in chronic urticaria are associated with altered gastroduodenal permeability. Allergy. 2004 Oct;59(10):1118-23.

42. Benitez-Del-Castillo JM1, Garcia-Sanchez J, Iradier T, Bañares A. Sulfasalazine in the prevention of anterior uveitis associated with ankylosing spondylitis. Eye (Lond). 2000 Jun;14 ( Pt 3A):340-3.

43. Goebel A, Buhner S, Schedel R, Lochs H, Sprotte G. Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome. Rheumatology (Oxford). 2008 Aug;47(8):1223-7. doi: 10.1093/rheumatology/ken140. Epub 2008 Jun 7.

44. Aguirre Valadez JM, Rivera-Espinosa L, Méndez-Guerrero O, Chávez-Pacheco JL, García Juárez I, Torre A. Intestinal permeability in a patient with liver cirrhosis. Ther Clin Risk Manag. 2016 Nov 18;12:1729-1748. eCollection 2016.

45. Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015 Oct 14;9:392. doi: 10.3389/fncel.2015.00392. eCollection 2015.

46. Cordain L. Cereal grains: humanity’s double edged sword. World Rev Nutr Diet 1999;84:19 –73.

47. Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006;41(4):408–419.

48. Bernardo D, Garrote JA, Fernández-Salazar L, et al. Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut. 2007;56(6):889–890.

49. Rakhimova M, Esslinger B, Schulze-Krebs A, et al. In vitro differentiation of human monocytes into dendritic cells by peptic-tryptic digest of gliadin is independent of genetic predisposition and the presence of celiac disease. J Clin Immunol. 2009;29(1):29–37.

50. Doherty M, Barry RE. Gluten-induced mucosal changes in subjects without overt small-bowel disease. Lancet. 1981;1(8219):517–520.

51. Reichelt KL, Jensen D. IgA antibodies against gliadin and gluten in multiple sclerosis. Acta Neurol Scand. 2004;110(4):239–241.

52. Pengiran Tengah CD, Lock RJ, Unsworth DJ, Wills AJ. Multiple sclerosis and occult gluten sensitivity. Neurology. 2004;62(12):2326–2327.

53. Barbeau WE, Bassaganya-Riera J, Hontecillas R. Putting the pieces of the puzzle together: a series of hypotheses on the etiology and pathogenesis of type 1 diabetes. Med Hypotheses. 2007;68(3):607–619.

54. Michaëlsson G, Gerdén B, Hagforsen E, et al. Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet. Br J Dermatol. 2000;142(1):44–51.

55. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000;83(3):207–217.

56. Keukens EA, de Vrije T, van den Boom C, et al. Molecular basis of glycoalkaloid induced membrane disruption. Biochim Biophys Acta. 1995;1240(2):216–228.

57. Gee JM, Wortley GM, Johnson IT, et al. Effects of saponins and glycoalkaloids on the permeability and viability of mammalian intestinal cells and on the integrity of tissue preparations in vitro. Toxicol In Vitro. 1996;10(2):117–128.

58. Alvarez JR, Torres-Pinedo R. Interactions of soybean lectin, soyasaponins, and glycinin with rabbit jejunal mucosa in vitro. Pediatr Res. 1982;16(9):728–731.

59. Chao AC, Nguyen JV, Broughall M, et al. Enhancement of intestinal model compound transport by DS-1, a modified Quillaja saponin. J Pharm Sci. 1998;87(11):1395–1399.

60. Story JA, LePage SL, Petro MS, et al. Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats. Am J Clin Nutr. 1984;39(6):917–929.

61. Johnson IT, Gee JM, Price K, Curl C, Fenwick GR. Influence of saponins on gut permeability and active nutrient transport in vitro. J Nutr. 1986 Nov;116(11):2270-7.

62. Scanu AM1, Bull TJ, Cannas S, Sanderson JD, Sechi LA, Dettori G, Zanetti S, Hermon-Taylor J. Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn’s disease and Johne’s disease: common neural and immune pathogenicities. J Clin Microbiol. 2007 Dec;45(12):3883-90. Epub 2007 Oct 3.

63. 12. Chacon, O., L. E. Bermudez, and R. G. Barletta. 2004. Johne’s disease, inflammatory bowel disease, and Mycobacterium paratuberculosis. Annu. Rev. Microbiol. 58:329-363.

64. Clarke, C. J. 1997. The pathology and pathogenesis of paratuberculosis in ruminants and other species. J. Comp. Pathol. 116:217-261.

65. Casu A, Pascutto C, Bernardinelli L, Songini M. Type 1 diabetes among sardinian children is increasing: the Sardinian diabetes register for children aged 0-14 years (1989-1999). Diabetes Care. 2004 Jul; 27(7): 1623-9.

66. Bruno G, Maule M, Biggeri A, et al. More than 20 years of registration of type 1 diabetes in Sardinian children: temporal variations of incidence with age, period of diagnosis, and year of birth. Diabetes 2013; 62(10): 3542-6.

67. Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205. doi: 10.1111/j.1749-6632.2009.04037.x.

68. Secondulfo M, Iafusco D, Carratù R, deMagistris L, Sapone A, Generoso M, Mezzogiomo A, Sasso FC, Cartenì M, De Rosa R, Prisco F, Esposito V. Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients. Dig Liver Dis. 2004 Jan;36(1):35-45.

69. Li N, Neu J. Glutamine deprivation alters intestinal tight junctions via a PI3-K/Akt mediated pathway in Caco-2 cells. J Nutr. 2009;139:710-4.

70. Hulsewe KW, van der Hulst RW, van Acker BA, von Meyenfeldt MF, Soeters PB. Inflammation rather than nutritional epletion determines glutamine concentrations and intestinal permeability. Clin Nutr. 2004;23:1209-16.

71. Lucendo AJ, De Rezende LC. Importance of nutrition in inflammatory bowel disease. World J Gastroenterol. 2009;15:2081-8.

72. Van der Hulst RR, von Meyenfeldt MF, van Kreel BK, Thunnissen FB, Brummer RJ, Arends JW, et al. Gut permeability, intestinal morphology, and nutritional depletion. Nutrition. 1998;14:1-6.

73. Potsic B, Holliday N, Lewis P, Samuelson D, DeMarco V, Neu J. Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology. Pediatr Res. 2002 Sep;52:430-6.

74. Li N, Lewis P, Samuelson D, Liboni K, Neu J. Glutamine regulates Caco-2 ll tight junction proteins. Am J Physiol Gastrointest Liver Physiol. 2004;287:G726-33.

75. Lima AA, Brito LF, Ribeiro HB, Martins MC, Lustosa AP, Rocha EM, et al. Intestinal barrier function and weight gain in malnourished children taking glutamine supplemented enteral formula. J Pediatr Gastroenterol Nutr. 2005;40:28-35.

76. Hulsewe KW, van Acker BA, Hameeteman W, van der Hulst RR, Vainas T, Arends JW, et al. Does glutamine-enriched parenteral nutrition really affect intestinal morphology and gut permeability? Clin Nutr. 2004;23:1217-25.

77. Coëffier M, Marion-Letellier R, Déchelotte P. Potential for amino acids supplementation during inflammatory bowel diseases. Inflamm Bowel Dis. 2010;16:518-24.

78. van den Berg A, van Zwol A, Moll HA, Fetter WP, van Elburg RM. Glutamine-enriched enteral nutrition in very low-birth-weight infants: effect on the incidence of allergic and infectious diseases in the first year of life. Arch Pediatr Adolesc Med. 2007;161:1095-101.

79. Roth E. Nonnutritive effects of glutamine. J Nutr. 2008;138:2025S-31S.