Leaky Gut Syndrome – causes, symptoms and routes to repair

The gut is often referred to as a foundation pillar of health for the body and the intestinal epithelium (barrier) plays a critical role in human health and disease.

In recent years there has been increasing recognition of an association between disrupted intestinal barrier function, also called leaky gut, and the development of a wide range of chronic diseases including autoimmune and inflammatory conditions. This blog will focus on the health of the gut lining and consider repair and prevention of leaky gut.

Skip to Key Takeaways

The intestinal tract

The intestinal tract contains the body’s largest interface between the internal and external environment and serves two opposite functions: it allows the absorption of needed nutrients from the intestinal lumen into the circulation and, on the other hand, prevents the penetration of harmful entities including microorganisms, antigens, and pro-inflammatory factors.1

The intestinal barrier

The intestinal barrier is a single-cell layer that constitutes the largest and most important barrier against the external environment. It covers a surface area of about 400 m² and requires about 40% of the body’s energy expenditure.2 It acts as a selectively permeable barrier permitting the absorption of nutrients, electrolytes and water, while maintaining an effective defence against gastrointestinal tract toxins, large peptides and gut flora. The epithelium maintains its selective barrier function through the formation of complex protein networks that mechanically link adjacent cells and seal the intercellular spaces (spaces between cells).3

The gut microbiome

The human gut is home to approximately 100 trillion microorganisms, collectively referred to as gut microbiota. Within the digestive tract, gut microbes promote peristalsis (the movement of food through the intestines), protect against infection, produce vitamins, and maintain a healthy gastrointestinal mucus layer and therefore have a profound impact on health.

Outside the digestive tract, gut microbes influence other organs and tissues through neural networks and signaling molecules. Through these complex communication networks, gut microbes regulate 70 to 80% of the immune system and therefore play a central role in immune system homeostasis.4

What is leaky gut?

Leaky gut, or increased intestinal permeability, is a condition in which the structural integrity of the gut barrier becomes compromised, allowing undigested food particles, large proteins and other molecules to escape from the gut into the blood.

The entry of undesirable and incompatible substances from the gut into the bloodstream (i.e. antigens) causes the immune system to launch an inflammatory response. Chronic inflammation resulting from leaky gut can therefore play a role in many chronic health conditions (as inflammation is a significant contributor to many disease conditions).

Signs and symptoms which may indicate possibility of leaky gut

The following conditions can potentially come about as a result of leaky gut:

  • Seasonal allergies or asthma5
  • Digestive issues such as bloating, diarrhoea or irritable bowel syndrome (IBS)6
  • Hormonal imbalances such as PMS or PCOS7
  • Depression, anxiety, ADD or ADHD8
  • Autoimmune disease such as rheumatoid arthritis or coeliac disease9,10
  • Chronic fatigue or fibromyalgia11
  • Skin issues such as acne or eczema12
  • Food allergies or food intolerances13

What causes leaky gut?

Leaky gut syndrome is usually provoked by exposure to substances which damage the integrity of the intestinal mucosa.

The commonest causes of damage are:

  • Candida overgrowth14 or other infectious agents (viral, bacterial, protozoan)15,16
  • Inflammatory bowel disease – such as Crohn’s disease17
  • Ethanol18
  • Coeliac disease19
  • Chemotherapy medicines20
  • Chronic kidney disease21
  • Non-steroidal anti-inflammatory drugs22

Other common causes are sugar and gluten. One study found that intestinal permeability was increased most dramatically by a high sugar diet.23


What is gluten?

Gluten is a protein made up of the peptides gliadin and glutenin and it is found in the grains wheat (including varieties such as spelt and kamut), rye and barley. Although oats do not naturally contain gluten they are often contaminated with gluten during farming processes.

When a food that contains gluten reaches the intestines, digestive enzymes break it down into the peptides gliadin and glutenin. As the peptides make their way through the digestive system, the gut-associated lymphoid tissue (GALT) reviews them for potentially harmful substances. GALT is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.

In people who have no issues with gluten, the peptides are absorbed. In people who have coeliac disease, the GALT identifies gliadin (or other peptides) as a dangerous substance and produces antibodies to attack it.

These antibodies also attack an enzyme in the gut called tissue transglutaminase (tTG) which has a similar appearance to gliadin. Tissue transglutaminase has a number of functions, but one of its roles is holding together the microvilli of the gut (the microvilli increase the surface area for absorption of nutrients). When attacked by anti-gliadin antibodies the microvilli can atrophy and erode, decreasing the ability to absorb nutrients and allowing the walls of the intestine to become leaky. This can manifest as digestive symptoms, including constipation, diarrhoea, bloating, weight loss, fat malabsorption and malnutrition, such as iron deficiency or anaemia and low vitamin D. This blunting of the microvilli is the hallmark of the autoimmune condition coeliac disease.

Other conditions associated with CD include dermatitis herpetiformis, a violent, blistering rash, or gluten ataxia, which may lead to neurological problems and loss of coordination. The only treatment for coeliac disease is total avoidance of gluten.

The prevalence of coeliac disease has increased significantly over the last 50 years. A 2009 study published in Gastroenterology showed that coeliac disease has increased from one in 650 people to one in 120 people over the last 50 years.24

There are also many people who do not have CD but still have a reaction to gluten – this is known as non-coeliac gluten sensitivity (NCGS). In this case when gluten is consumed it can cause irritation and inflammation of the digestive system, leading to unpleasant digestive symptoms such as bloating, diarrhoea, constipation, fullness and discomfort. Non-coeliac gluten sensitivity can also cause or contribute to non-gastrointestinal symptoms such as autoimmunity, allergic and atopic conditions such as hay fever, mental health disorders and other inflammatory conditions.


Gluten also causes the gut cells to release a protein called zonulin. Zonulin’s role is to open up the spaces between the cells of the intestinal lining; this is a process that is essential for the efficient absorption of some nutrients.25 Thus zonulin is an enzyme that modulates the permeability of tight junctions between cells of the wall of the digestive tract.

When gliadin from wheat gluten interacts with the CXCR3 receptors on cells in the small intestine, the cells produce and release zonulin. Zonulin then reacts with the gastrointestinal cells, causing the gut’s tight junctions to grow wider.26 With the gut tight junctions widened, molecules that are usually too big to fit through can freely flow in and out of the gut. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance.27 When the finely tuned zonulin pathway is dysregulated, the gut cells remain open allowing much larger molecules to enter the blood stream and this is referred to as leaky gut. This can, in time, lead to both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders.


Leaky gut is known to have a strong association with Candida overgrowth. Candida albicans is part of the natural microflora. It can be found in the gastrointestinal tract, the mouth, and the vagina.

The Candida cells begin to cause problems when they adopt their fungal form and begin to grow hyphae – the long branches that grow out of the fungus. These branches invade the cells in the intestinal lining, creating inflammation and permeating the membrane that normally prevents substances from leaking out.


Non-steroidal anti-inflammatory (NSAIDs) drugs (Ibuprofen, Naproxen, high-dose aspirin etc) can cause leaky gut because they inflame the intestinal lining, causing a widening of the spaces between cells and sometimes intestinal bleeding.

Antibiotics create their damage by destroying beneficial bacteria. These bacteria perform hundreds of functions required for healthy metabolism and immune response; and post-antibiotics opportunistic species such as Candida albicans and other pathogenic fungi and yeast may overgrow and cause symptoms.

Beneficial gut bacteria have an important role in reducing the toxicity of bile when it enters the small intestine. Bile is extremely damaging to the large intestine epithelium. However, this process is compromised post antibiotics and the bile salts freely enter and damage the large intestine.

The 5-R Protocol for Healing a Leaky Gut

Nutritional therapists use a systematic and comprehensive 5 step programme to heal a leaky gut called the 5-R programme, developed by Dr Jeffrey Bland.


This involves identifying and removing factors that may be contributing to poor gut health and imbalanced gut flora:

  • Avoid all gluten containing foods, sugar, alcohol, conventional dairy products and any other known food sensitivities.
  • Reduce stress – stress triggers the release of the hormone cortisol into the blood stream. Too much cortisol can cause inflammation in the digestive tract.
  • Remove infections – undesirable microbes. If there is an overgrowth of undesirable bacteria, protozoa or yeast, this will also need to be addressed using appropriate anti-microbials.


This refers to replacing factors that may be missing to support good digestive function (e.g. hydrochloric acid, digestive enzymes, supporting bile production). It could also refer to replacing nutrients that are needed to support the digestive and immune systems.

Supplements may be used to bridge the nutrition gap; to replace elements such as betaine HCL, bile salts, and enzymes that help digest fat, carbohydrates and protein. Foods that support digestion such as bitter foods to stimulate stomach acid and digestive enzymes may be included.

Other supplements to address sub-optimal levels of nutrients or nutrient deficiencies.  Digestive conditions can affect the absorption of nutrients such as B12, iron, calcium, magnesium and zinc.


It is essential to rebalance the gut flora to ensure adequate numbers of friendly gut microbes and prevent overgrowth of dysbiotic species.

Prebiotic foods – This term describes the type of food that gut bacteria love to eat.  They include specific types of carbohydrate fibre found in onions, garlic, leeks, asparagus, dark green leafy vegetables, chicory and apples. Foods rich in polyphenols also encourage a healthy bacterial balance e.g. cacao, olive oil, coffee (fresh, organic) and tea.

Probiotic foods – rich in bacteria beneficial for the digestive system.  A probiotic supplement can be taken as well as using fermented foods such as yoghurt, sauerkraut, kimchi and kombucha.


At this stage we want to create an environment that supports gut-healing and long-term relief, encouraging repair of the intestinal cells and mucosa, and continuing to reduce inflammation. This may include:

  • Foods rich in amino acids such as bone broth
  • Supplements such as L-glutamine, collagen, Aloe vera, marshmallow, slippery elm, curcumin, lactoferrin, essential fatty acids, vitamins A, C, D, E and zinc


Lifestyle habits have enormous influence on the digestive system and health.  Rebalance refers to considering other lifestyle factors and behaviours to change – so giving consideration to:

  • Stress management
  • Improving sleep
  • Moving more (or less, if necessary – prolonged very high intensity exercise without adequate recovery may have negative effects on the gut)
  • Improving relationships

While this is presented as a step by step protocol, multiple phases may be carried out at the same time.   For example, removing irritating foods, compounds and pathogens from the digestive tract is the first step and will also initiate the repair phase.


“All disease begins in the gut.” — Hippocrates

Hippocrates made this profound statement more than 2,000 years ago, however, it is only recently that practitioners have appreciated just how right he was. Gut health is critical to overall health, and an unhealthy gut contributes to a wide range of chronic diseases, including diabetes, obesity, autism, depression, and anxiety. Many people believe that supporting intestinal health and restoring the integrity of the gut barrier are two of the most important factors to begin a return to health.

Key Takeaways

  • The intestinal tract contains the body’s largest interface (and barrier) between the internal and external environment.
  • Leaky gut is a condition in which the structural integrity of the gut barrier becomes compromised, allowing undigested food particles and other molecules to escape from the gut into the blood. These macromolecules trigger inflammation and can lead to the development of many diseases including autoimmune disease.
  • Many factors can contribute to the development of leaky gut including the composition of the gut microflora (i.e. overgrowth of undesirable microbes), food sensitivities (gluten and others), high sugar diet, alcohol, stress, antibiotics and other medications.
  • Gluten is a protein made up of the peptides; gliadin and glutenin and it is found in many grains such as wheat, rye and barley. In people who have no issues with gluten, the peptides are absorbed. In people who have coeliac disease or gluten sensitivity, gliadin and other gluten peptides may contribute to leaky gut.
  • Non-steroidal anti-inflammatory (NSAIDs) drugs (Ibuprofen, Naproxen, high-dose aspirin etc) can cause leaky gut because they inflame the intestinal lining, causing a widening of the spaces between cells.
  • Antibiotics create damage by destroying beneficial bacteria. These bacteria perform hundreds of functions required for healthy metabolism and immune response; and post-antibiotics opportunistic species such as Candida albicans and other pathogenic fungi and yeast may overgrow and cause symptoms.
  • Nutritional therapists use a 5-R programme to support gut healing and a return to health; the 5 Rs are i) Remove – identify and remove triggering factors that are contributing to leaky gut; ii) Replace – add in appropriate support e.g. digestive enzymes/hydrochloric acid etc. if needed; iii) Reinoculate – with prebiotics and probiotics; iv) Repair – nutrients to support the gut lining; and v) Rebalance – consider other lifestyle factors such as sleep and physical activity.

If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Jackie) by phone or email at any time.

jackie@cytoplan.co.uk, 01684 310099

Jackie Tarling and the Cytoplan Editorial Team


  1. Assimakopoulos SF, Triantos C, Maroulis I, Gogos C. The Role of the Gut Barrier Function in Health and Disease. Gastroenterol Res. 2018;11(4):261-263. doi:10.14740/gr1053w
  2. Bischoff SC, Barbara G, Buurman W, et al. Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189. doi:10.1186/s12876-014-0189-7
  3. Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124(1):3-20; quiz 21-22. doi:10.1016/j.jaci.2009.05.038
  4. Vighi G, Marcucci F, Sensi L, Di Cara G, Frati F. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008;153 Suppl 1(Suppl 1):3-6. doi:10.1111/j.1365-2249.2008.03713.x
  5. Farshchi MK, Azad FJ, Salari R, Mirsadraee M, Anushiravani M. A Viewpoint on the Leaky Gut Syndrome to Treat Allergic Asthma: A Novel Opinion. J Evid Based Complementary Altern Med. 2017;22(3):378-380. doi:10.1177/2156587216682169
  6. Gecse K, Róka R, Séra T, et al. Leaky Gut in Patients with Diarrhea-Predominant Irritable Bowel Syndrome and Inactive Ulcerative Colitis. Digestion. 2012;85(1):40-46. doi:10.1159/000333083
  7. Lindheim L, Bashir M, Münzker J, et al. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study. Yu Y, ed. PLoS One. 2017;12(1):e0168390. doi:10.1371/journal.pone.0168390
  8. Martin CR, Osadchiy V, Kalani A, Mayer EA. The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol. 2018;6(2):133-148. doi:10.1016/j.jcmgh.2018.04.003
  9. Hollander D. Intestinal permeability, leaky gut, and intestinal disorders. Curr Gastroenterol Rep. 1999;1(5):410-416. doi:10.1007/s11894-999-0023-5
  10. Fasano A. Leaky Gut and Autoimmune Diseases. Clin Rev Allergy Immunol. 2012;42(1):71-78. doi:10.1007/s12016-011-8291-x
  11. Maes M. Leaky gut in chronic fatigue syndrome: A review.
  12. Salem I, Ramser A, Isham N, Ghannoum MA. The Gut Microbiome as a Major Regulator of the Gut-Skin Axis. Front Microbiol. 2018;9:1459. doi:10.3389/fmicb.2018.01459
  13. Jackson P., Baker RW., Lessof M., Ferrett J, Macdonald D. INTESTINAL PERMEABILITY IN PATIENTS WITH ECZEMA AND FOOD ALLERGY. Lancet. 1981;317(8233):1285-1286. doi:10.1016/S0140-6736(81)92459-4
  14. James A. Jackson, Ph.D. B, Hugh D. Riordan MD;., Ronald Hunninghake MD;., Chris Revard B. Candida Albicans: The Hidden Infection.
  15. Gibson PR. Increased gut permeability in Crohn’s disease: is TNF the link? Gut. 2004;53(12):1724-1725. doi:10.1136/gut.2004.047092
  16. Lahesmaa-Rantala R, Magnusson KE, Granfors K, Leino R, Sundqvist T, Toivanen A. Intestinal permeability in patients with yersinia triggered reactive arthritis. Ann Rheum Dis. 1991;50(2):91-94. doi:10.1136/ard.50.2.91
  17. Serrander R, Magnusson K-E, Sundqvist T. Acute Infections with Giardia lamblia and Rotavirus Decrease Intestinal Permeability to Low-Molecular Weight Polyethylene glycols (PEG 400). Scand J Infect Dis. 1984;16(4):339-344. doi:10.3109/00365548409073958
  18. Bjarnason I, Peters TJ, Wise RJ. The leaky gut of alcoholism: possible route of entry for toxic compounds. Lancet (London, England). 1984;1(8370):179-182. doi:10.1016/s0140-6736(84)92109-3
  19. Perry I, Iqbal T, Cooper B. Intestinal permeability in coeliac disease. Lancet (London, England). 2001;358(9294):1729-1730. doi:10.1016/S0140-6736(01)06750-2
  20. Lifschitz CH, Mahoney DH. Low-Dose Methotrexate-Induced Changes in Intestinal Permeability Determined by Polyethylene Glycol Polymers. J Pediatr Gastroenterol Nutr. 1989;9(3):301-306. doi:10.1097/00005176-198910000-00007
  21. Anders H-J, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 2013;83(6):1010-1016. doi:10.1038/KI.2012.440
  22. Bjarnason I, Zanelli G, Prouse P, Williams P, Gumpel MJ, Levi AJ. Effect of Non-Steroidal Anti-Inflammatory Drugs on the Human Small Intestine. Drugs. 1986;32(Supplement 1):35-41. doi:10.2165/00003495-198600321-00007
  23. Pereira MT, Malik M, Nostro JA, Mahler GJ, Musselman LP. Effect of dietary additives on intestinal permeability in both Drosophila and a human cell co-culture. Dis Model Mech. 2018;11(12). doi:10.1242/dmm.034520
  24. Rubio–Tapia A, Kyle RA, Kaplan EL, et al. Increased Prevalence and Mortality in Undiagnosed Celiac Disease. Gastroenterology. 2009;137(1):88-93. doi:10.1053/j.gastro.2009.03.059
  25. Lammers KM, Lu R, Brownley J, et al. Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3. Gastroenterology. 2008;135(1):194-204.e3. doi:10.1053/j.gastro.2008.03.023
  26. 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;1165:195-205. doi:10.1111/j.1749-6632.2009.04037.x
  27. Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012;1258(1):25. doi:10.1111/J.1749-6632.2012.06538.X

Last updated on 9th November 2022 by cytoffice


7 thoughts on “Leaky Gut Syndrome – causes, symptoms and routes to repair

  1. A very timely read. My son and I are both on the Fodmap diet as we both have IBS. My son was recently diagnosed and I was diagnosed when I was his age (24)
    Your article give clear helpful and up to date explanations to what the problems are with our guts. Thank you

  2. My wife has been advised to follow a Fodmap diet but she has been advised not to have onions, asparagus, and apples amongst others?

    1. Hi Nigel,

      Thank you for your comment.
      FODMAP stands for “fermentable oligo-, di-, mono-saccharides and polyols.” These are small carbohydrates that many people cannot digest — particularly those with irritable bowel syndrome (IBS).
      The key principle of the diet is that foods high in specific fermenting short-chain carbohydrates (FODMAPs), that are either: indigestible (lactose, fructans, galactans) or slowly absorbed from the small intestine (fructose, sorbitol, mannitol) are removed from the diet. These carbohydrates can cause digestive problems in some people and their removal can relieve their symptoms. Studies have shown strong links between FODMAPs and digestive symptoms like gas, bloating, stomach pain, diarrhoea and constipation.
      The foods you mention are high FODMAPS.
      This diet is usually followed for a short period of time to identify foods that are responsible for symptoms and we recommend anyone following it does so under the supervision of a qualified nutritional therapist.

      Best wishes,

  3. Hello good morning, this blog is perfectly timed. I love the layout of the lesson and the way you teach the information. I’ve been suffering from Candida for years now (on and off) and recently purchased supplements from you. The Cyto-protect, Caprylic Acid and Cyto-zyme will be my next purchase today. Terri

  4. The only issue I have with this article is that autism is classed as a disease. It isn’t. Nor is asd a mental health issue, although the condition can and does affect mental health, so secondary issues like anxiety and depression often impact on a person who is autistic. It’s a very wide spectrum; as far as I’m aware there are no therapies or medication or lifestyle choices that can change or cure what is, effectively a neurological condition where the brain is hardwired in a different way from neuro typical brains. So, while diet and lifestyle choices may have a positive impact on the anxiety, depression, insomnia etc etc etc that an autistic person has to endure, it will not change the fact that they are autistic, and it will vary from person to person depending on where they are on the spectrum. There is, as yet, no cure for autism.

    1. Hi Anne-Marie,

      Thank you for your comment. We understand the “cure” may well not be possible as the susceptibility and “hard wiring” cannot be changed. However, diet and lifestyle changes have been shown to modify the expression and impact of the symptoms of the condition on daily life. The extent of the benefit of diet and lifestyle changes will vary in different individuals, as the collective totality of the symptoms in an individual will have a number of different genetic and non-genetic drivers, some of which are more able to be modified by diet, lifestyle and environmental factors than others. The feedback from medical Doctors working in a complementary way with autistic spectrum disorders unequivocally is that a thoughtful, knowledge, personalized approach almost always gives a noticeable benefit.


  5. Unfortunately, I’d love to read this but, due to dyslexia and fibromyalgia, reading from a screen is too exhausting for me.
    I have leaky gut, IBS, and gastroparesis. In desperation, I saw a private doctor who recommended Cytoplan and various supplements. I am currently in a bad flare but, so long as I stay in the fodmap diet, and take my supplements, I can at least get on top of my leaky gut and gastroparesis symptoms, often for several weeks at a time. I’ve spent a fortune at Cytoplan but it’s worth it.
    My one complaint is the huge waste of plastic when the pots aren’t even a quarter full – smaller pots please! Or better still, a more environmentally-friendly option!

We'd love your comments on this article
It's easy, just post your questions, comments or feedback below

Names will be displayed as entered. Your email address will not be published. Required *