What is leaky gut syndrome?
Leaky gut syndrome, commonly referred to as "gastrointestinal permeability”, is a condition in which the epithelial cells that constitute the ‘wall’ of the small intestine become loose and hyperpermeable.1 This forms passages that allow undigested food, bacteria, toxins and allergens to 'leak' through the intestines and into the bloodstream.2 Upon entering the blood, these harmful substances trigger inflammatory and allergenic responses. If the digestive mucosal epithelia lose their protective function, it could impair autoimmune development.2 Thus, a healthy gut lining is pivotal for gut health.
There are several believed causes of leaky gut syndrome. Examples include:
- Inflammatory states such as Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), celiac disease, colitis and neoplasia3
- Excessive alcohol intake4
- Chronic overuse of NSAIDs such as ibuprofen, indomethacin or aspirin5,6
- Gut dysbiosis via dietary changes or antibiotic use7,8
- Excessive intake of sugars and refined carbohydrates4,7,9
- Nutrient deficiencies in vitamin B12, vitamin C, vitamin D and zinc 10, 11, 12, 13
What happens when you have a leaky gut?
The intestinal wall selectively absorbs essential nutrients, ions and compounds whilst serving as a barrier against harmful substances. The systemic effect of microbial toxins and pathogens that ‘leak’ through this wall includes a subsequent immune response and the production of inflammatory mediators, namely Cytokines. Gastrointestinal permeability has been linked to inflammatory bowel diseases (IBDs) like Crohn’s disease and autoimmune diseases.2
A leaky gut directly impacts your digestion and immune responses. Intestinal permeability associated with a leaky gut leads to other symptoms, including food sensitivities, allergies, bloating, abdominal pain and indigestion. These shared symptoms indicate other underlying health issues. However, it is essential to note that these symptoms do not always suggest leaky gut syndrome is the cause. Depending on this underlying cause, different symptoms of a leaky gut will be present.
The link between leaky gut syndrome and other health issues
In areas where harmful substances have ‘leaked through’ the intestinal barrier, macrophages and lymphocytes release inflammatory cytokines to ‘clean up’ those substances. The local accumulation of low molecular weight catabolic products near the gastrointestinal tract attracts additional fluid and white blood cells, with or without heat release sufficient for significant tissue temperature elevation. This causes inflammation of the surrounding tissue, forming the basis of IBDs. In the case of Coeliac Disease, for example, the accumulation of gluten in the blood induces cytokine release. This activates an autoimmune response whereby the body ‘attacks’ the cells that constitute the intestinal wall.
Medical professionals must collate evidence to determine whether a leaky gut should be classified as a cause or a disease symptom. Thus far, research has demonstrated intestinal permeability as a symptom of chronic diseases such as IBD and IBS, as well as indicating early-onset disease development.14, 15,16, 17 Whilst evidence suggests that increased intestinal permeability has microbiome, autoimmune, metabolic and inflammatory implications, it is challenging to conclude leaky gut is a root cause of disease.18 The 2019 Journal of ‘Gut’ suggests that a leaky gut may cause disease, and subsequent gut dysbiosis leads to inflammatory diseases and their severity.19 Similarly, a recent article in the ‘Journal of Nutrients’ writes that disruptions to the structure of the intestinal barrier are possible causes of celiac disease but not a definite cause.20
In general, current findings should serve as a framework for future development of hypotheses (that is, is leaky gut a cause or an effect of certain diseases?), as the evidence to prove leaky gut as the underlying cause is insufficient.
Symptoms to indicate a leaky gut
The symptoms of a leaky gut depend on the underlying cause. Common symptoms include:
Digestive issues include abdominal pain, diarrhoea, bloating, gas, weight loss and constipation. Increased gut permeability has also been linked to the development of IBS and is evident in those with non-celiac gluten sensitivity.2
When the oestrogen/progesterone balance is disrupted, oestrogen dominance occurs, which has been shown to increase the permeability of the intestinal wall.21
Autoimmune diseases such as coeliac disease, type 1 diabetes, multiple sclerosis, IBD and rheumatoid arthritis are characterised by increased intestinal permeability that allows the passage of antigens from the intestinal flora.2
Chronic fatigue or fibromyalgia
Intracellular inflammation, systemic inflammation, and increased levels of inflammatory cytokines associated with leaky gut syndrome are novel pathways in chronic fatigue syndrome (CFS).22 In a study published in 2015, those with fibromyalgia were at 1.5 times greater risk of IBS, of which the symptoms included chronic abdominal pain, diarrhoea and constipation.23
Food allergies or sensitivities
Food allergies are one of the most common symptoms of a leaky gut.24 Digestive issues, including Crohn’s Disease and Celiac disease, have been closely linked to food sensitivities (gluten) and allergies (dairy allergies).25
Systemic inflammation triggers autoimmune conditions such as Ankylosing spondylitis (AS), creating inflammation in the spinal joints and causing chronic back pain and stiffness.2
Diagnosis for leaky gut syndrome
The standard test for leaky gut syndrome is the mannitol and lactulose test.26 This test analyses urine to highlight the presence of two sugars, lactulose and mannitol, whereby significantly greater concentrations of these sugars indicate a leaky gut.27 For this test, a person drinks a sugar solution. Urine is collected, and the concentration of lactulose and mannitol reflects how much is absorbed by the body. A test that indicates a ‘healthy’ gut shows high concentrations of mannitol and low lactulose concentrations. If both sugars are elevated, the intestinal lining is likely hyper-permeable, suggesting a leaky gut. If low concentrations are found, the individual may suffer from nutrient malabsorption.
Blood tests for Zonulin could also be considered. Discovered by Alessio Fasano in 2000, Zonulin is a protein that modulates the permeability of tight junctions between the cells that constitute the intestinal wall. Zonulin can be used as a biomarker of impaired intestinal barrier function for leaky gut.18 Faso found that high levels of Zonulin increased gut permeability which may further contribute to the development of chronic inflammation.
You may wish to have an IgG food antibody test. Evidence of this antibody can indicate food sensitivity.
Treatment for a leaky gut syndrome
Few indicators to show that leaky gut is fixed
Indicators that your leaky gut is healing will depend on your initial symptoms. Suppose you find that general bowel movement is becoming more regulated, and you no longer experience or have less frequent bouts of constipation and diarrhoea. In this case, your leaky gut is likely healing.
Another indicator that your leaky gut is healing is if your food sensitivities go away. Certain foods trigger all sorts of inflammatory responses throughout the body. Once these are removed, they mustn’t be reintroduced. After all, once a leaky gut is healed, you want to maintain it!
Whether you are experiencing acne, eczema, psoriasis, rashes or rosacea, skin issues are an external indication of an internal problem in the gut. Your skin issues may subside as you heal your leaky gut.28
Foods to avoid if you have a leaky gut syndrome
The treatment for leaky gut involves a healthy diet. A standard initial step of treatment is to remove foods that can be inflammatory and introduce ‘gut-friendly’ foods. Inflammatory foods include:
- Alcohol and Carbonated drinks
- Artificial Sweeteners
- Dairy products
- Baked goods such as pastries, bread and sweet goods
- Gluten-based products such as pasta, bread and rice
- Vegetable oils
- Processed foods
- Nuts, particularly those that undergo processing with additional sugar, salt and vegetable oils
- Sauces and dressings. These often contain salicylates, harsh chemicals on the gut that can exacerbate skin issues.
Incorporate ‘gut-friendly’ foods that are anti-inflammatory.
- Turmeric has anti-inflammatory properties that help minimise local and systemic inflammation.
- Fermented foods and vegetables, such as kimchi and sauerkraut, have probiotic benefits, which bring ‘good bacteria’ to the digestive system, and help keep the 'bad bacteria' at bay.
- Choose a diet with a wide variety of fresh vegetables and plenty of leafy greens.
- Fruits with a Low Glycemic Index should be eaten in small amounts to prevent potentially harmful glucose spikes.
- Virgin olive oil has a high concentration of healthy fats, antioxidants and phenolic compounds that exert anti-inflammatory effects.
- Bone broth is rich in essential minerals that help reduce inflammation of the gut.
When to seek medical help
You should seek medical attention when:
- The discomfort interferes with daily activities
- Your abdominal area is tender or swollen
- Discomfort or abdominal pain persists for several days
- You experience persistent acid reflux that becomes increasingly severe
- It is painful to pass stool, often accompanied by blood.
In summary, a leaky gut, also known as intestinal permeability, is a disruption of the intestinal lining, or where tight junctions permit particles to 'leak' out of the digestive system and into the bloodstream. It is not yet recognised as a diagnosis in conventional medicine. Yet, several studies have looked into its effect on several diseases.
Several causes of a leaky gut can lead to various symptoms. These symptoms range from autoimmune diseases, such as Celiac Disease, to food sensitivities and skin issues.
You may be instructed to make beneficial lifestyle changes that help alleviate symptoms and heal your gut. These might include:
- Dietary changes that include increasing fibre intake and decreasing intake of sugar, refined carbohydrates and inflammatory foods
- Limit alcohol intake
- Regular administration of probiotics that help restore the gut flora
- Nutrient supplementation
- Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology. 1995;108(5):1566–1581.
- Fasano A. Leaky Gut and Autoimmune Diseases. Clinical Reviews in Allergy & Immunology. 2012;42:71–78.
- Hietbrink F, Besselink MG, Renooij W, de Smet MB, Draisma A, van der Hoeven H, et al. Systemic inflammation increases intestinal permeability during experimental human endotoxemia. Shock. 2009;32(4):374–378.
- Thuy S, Ladurner R, Volynets V, et al. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. Journal of Nutrition. 2008;138:1452-1455.
- Hollander D. Intestinal permeability, leaky gut, and intestinal disorders. Current Gastroenterology Reports. 1999;1(5):410–416.
- Kiefer D, Ali-Akbarian L. A BRIEF EVIDENCE-BASED REVIEW OF TWO GASTROINTESTINAL ILLNESSES: IRRITABLE BOWEL AND LEAKY GUT SYNDROMES. Integrative Medicine. 2004;3(3).
- Binienda A, Twardowska A, Makaro A, Salaga M. Dietary Carbohydrates and Lipids in the Pathogenesis of Leaky Gut Syndrome: An Overview. International Journal of Molecular Sciences. 2020;21(21):8368.
- Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Frontiers in immunology. 2017:598.
- Purdy M. Modulating the Bidirectional Communication of the Gut-Brain Axis in Times of Stress with Lactobacillus plantarum DR7. Alternative Therapies in Health and Medicine. 2021;27:134-7.
- Sturniolo GC, Di Leo V, Ferronato A, D’Odorico A, D’Incà R. Zinc supplementation tightens “leaky gut” in Crohn’s disease. Inflammatory bowel diseases. 2001;7(2):94-98.
- Grant R. Leaky Gut Syndrome Treatment: How to Heal Leaky Gut Syndrome Naturally. Lulu Press, Inc. 2014 Oct 13.
- Peluso I, Villano VD, Roberts AS, Cesqui E, Raguzzini A, Borges G, et al. Consumption of mixed fruit-juice drink and vitamin C reduces postprandial stress induced by a high fat meal in healthy overweight subjects. Current Pharmaceutical Design. 2014;20(6):1020-1024.
- Lobo de Sá FD, Backert S, Nattramilarasu PK, Mousavi S, Sandle GI, Bereswill S, et al. Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni. International Journal of Molecular Sciences. 2021;22(16):8872.
- Villani AC, Lemire M, Thabane M, Belisle A, Geneau G, Garg AX, et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology. 2010;138(4):1502-1513.
- Gradel KO, Nielsen HL, Schønheyder HC, Ejlertsen T, Kristensen B, Nielsen H. Increased short-and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology. 2009;137(2):495-501.
- De Kort S, Keszthelyi D, Masclee AA. Leaky gut and diabetes mellitus: what is the link?. Obesity Reviews. 2011;12(6):449-458.
- Kumar J, Kumar M, Pandey R, Chauhan NS. Physiopathology and management of gluten‐induced celiac disease. Journal of Food Science. 2017;82(2):270-277.
- Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Research. 2020;9.
- Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut. 2019;68(8):1516-1526.
- Drabińska N, Krupa-Kozak U, Jarocka-Cyrta E. Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet - Results of a Randomized, Placebo-Controlled, Pilot Trial. Nutrients. 2020;12(6):1736.
- Zhou Z, Zhang L, Ding M, Luo Z, Yuan S, Bansal MB, et al. Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues. Clinical immunology. 2017;183:174-180.
- Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuroendocrinology Letters. 2008;29(6):902.
- Yang TY, Chen CS, Lin CL, Lin WM, Kuo CN, Kao CH. Risk for irritable bowel syndrome in fibromyalgia patients: a national database study. Medicine (Baltimore). 2015;94(10):616.
- Simeonova D, Ivanovska M, Murdjeva M, Carvalho AF, Maes M. Recognizing the leaky gut as a trans-diagnostic target for neuro-immune disorders using clinical chemistry and molecular immunology assays. Current Topics in Medicinal Chemistry. 2018;18(19):1641-1655.
- Muthuirulan P. Leaky Gut Syndrome: Mystery Illness Triggered by Candida albicans. Journal of Nutritional Health & Food Engineering. 2016;4:448-9.
- Sequeira IR, Lentle RG, Kruger MC, Hurst RD. Standardising the lactulose mannitol test of gut permeability to minimise error and promote comparability. PloS One. 2014;9(6):e99256.
- Resnick RH. Lactulose Leaves the Leaky Gut. Inflammatory Bowel Diseases, 1996;2(3):223–224.
- Lio PA, Lal K. Leaky Gut and Atopic Dermatitis: Does the Concept Hold Water or Is Is Full of Holes? [Internet]. 2016 [updated 2021 Jul 15; cited 2022 Jul 04]. Available from: https://nationaleczema.org/blog/leaky-gut/