Leaky Gut Syndrome

Written by Vivienne Palin

     My STEAM project takes a look at leaky gut syndrome and covers the objective “Describe the 4 general layers of the digestive system and their function.”

     Everyone’s guts are naturally semi-permeable; this allows absorbed water and nutrients to enter the bloodstream and be delivered to different cells throughout the body (“Leaky Gut Syndrome,” n.d.). Leaky gut syndrome, more formally called increased intestinal permeability, is a condition in which the gastrointestinal mucosal lining of the gut becomes more permeable than normal, allowing large undigested molecules and pathogens to enter the bloodstream. This causes symptoms such as bloating, indigestion, fatigue, abdominal pain, and food and environmental allergies and sensitivities – some of the symptoms that are commonly associated with leaky gut (“11 Symptoms and Causes of Leaky Gut Syndrome,” 2019). The word “gut” refers to the gastrointestinal (GI) tract, also called the alimentary canal, which is a one-way tube that includes the pharynx, esophagus, stomach, and small and large intestines (Anatomy and Physiology 2e, 2022); however, when it comes to leaky gut syndrome, we’re zeroing in on the mucosal lining of the small intestine. There are four main layers that are constant throughout the gastrointestinal tract, starting from the innermost layer surrounding the lumen and moving outwards: the mucosa, submucosa, muscularis, and serosa. The mucosa layer of the small intestine can be further divided into another three layers: epithelium, lamina propria, and muscularis mucosae. These three layers form the intestinal barrier. The muscularis mucosae, the outermost mucosal layer, is comprised of a thin layer of smooth muscle that pulls the mucosa into undulating folds, such as circular folds, villi, and microvilli. These folds play a major role in digestion and absorption, as they greatly increase the surface area of the mucosa, allowing for more available area for digestion and absorption to take place (Anatomy and Physiology 2e, 2022). The lamina propria of the mucosa contains structural protein molecules, nerves, veins, and lymphocytes, which make up the mucosa-associated lymphoid tissue, or MALT (Anatomy and Physiology 2e, 2022). The epithelial layer of the small intestine, or intestinal epithelium, is comprised of simple columnar epithelium held closely together by tight junctions and mucus-secreting goblet cells. It is also enriched with different strains of bacteria, namely Lachnospiraceae, Bifidobacterium bifidum, Bifidobacterium longum, Ruminococcaceae, and the phylum Verrucomicrobia (Di Vincenzo et. al, 2024), which act as the first line of defense against both commensal and invading microbes (Sicard et. al, 2017). Mucus secreted by the goblet cells serves as the first physical defense in the barrier, and prevents antigens, toxins and bacteria from directly contacting the epithelial cells (Camilleri, 2020). The tight junctions act as a gate to keep passing substances inside the gut. However, bacterial infections, chronic stress, oxidative stress, poor food choices, use of medication, alcohol or chronic allergen exposure, and dysbiosis can cause this area to become irritated and inflamed (Di Vincenzo et. al, 2024). When this happens, the junctions loosen up, allowing larger molecules to pass through (Lipski, 2013, p. 41). These larger molecules that have now penetrated the gastrointestinal mucosal lining enter directly into the bloodstream. The body views these molecules, that are normally kept within the gut, as foreign, and an antibody response is activated. The intestinal lining becomes further damaged due to the inflammation and irritation, and as time goes by, larger and larger molecules are let through, as are disease-causing bacteria, fungi, and potentially toxic molecules, triggering antibody reactions over and over again (Lipski, 2013, p. 42). This is what is called leaky gut.

     To better understand the difference between a normal, healthy gut and a damaged, leaky gut, it can help to think of it as an analogy of two sets of gates. The first gate, the “healthy gut” gate, is tightly sealed and only allows qualified personnel (relating to certain substances) to pass through. The second gate, or the “leaky gut” gate, isn’t tightly sealed, and anyone, whether qualified or not, can pass through (relating to large, undigested molecules and pathogens). 

     There are many different causes for leaky gut syndrome. This is because leaky gut isn’t a disease or an illness; as we’ve seen above, it’s a symptom of inflammation and imbalance (Lipski, 2013, p. 41). There are many different health conditions and diseases that can be associated with leaky gut syndrome, such as allergies, sensitivities, intolerances, celiac disease, Crohn’s disease, Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), diabetes, asthma, eczema, rheumatoid arthritis, and the list goes on. When looking into treatment for leaky gut, especially if one has developed a medical condition because of it, it is important to figure out the underlying cause of the impermeability. For example, leaky gut caused by over-excessive alcohol consumption would be treated differently than leaky gut caused by an overgrowth of harmful bacteria in the gut. For this reason, treatment for leaky gut syndrome is dependent on its causative agent, and treatment modalities can vary quite a bit.

     Testing for leaky gut syndrome includes blood, stool, urine, and breath tests. Leaky gut blood tests typically look at different antibody markers, serum zonulin, and zonulin antibody levels, as zonulin is one of the proteins that regulates tight junctions in the intestines; if zonulin levels are high in the blood, it can suggest that the gut is more permeable than it should be. Leaky gut stool tests are also used for measuring zonulin levels. Urine tests for leaky gut are a little different from the two types of tests already mentioned. For the urine test, one would drink a solution called PEG 400, which contains substances with 11 different molecular weights. After six hours of urine collection, a lab analysis would measure how of each substance ended up in the urine, which would indicate how impermeable one’s gut is – the larger the molecular weights in the urine, the leakier the gut. The breath test, such as a hydrogen and methane breath test, is used to check for small intestine bacterial overgrowth, or SIBO, which could cause leaky gut. However, this test alone isn’t enough to diagnose leaky gut syndrome (Lawson, 2024). A tissue biopsy or confocal endomicroscopy, which are used to measure or look for permeability in gut tissue, respectively, may also be used in the diagnosis of leaky gut (Jones, 2025).

Summary: 

Leaky gut syndrome, also called increased intestinal permeability, is a condition in which the gastrointestinal mucosal lining of the gut becomes more permeable than normal. This allows large undigested molecules and pathogens to enter the bloodstream, causing antibody reactions and symptoms such as bloating, indigestion, fatigue, abdominal pain, and food and environmental allergies and sensitivities (“11 Symptoms and Causes of Leaky Gut Syndrome,” 2019). Leaky gut is a symptom of inflammation and imbalance, not a disease in itself (Lipski, 2013, p. 41). There are many different causes of increased intestinal impermeability, including bacterial infections, chronic stress, oxidative stress, poor food choices, use of medication, alcohol or chronic allergen exposure, and dysbiosis, which can cause this area to become irritated and inflamed (Di Vincenzo et. al, 2023). Treatment is dependent on the cause of the intestinal permeability. Testing for leaky gut syndrome includes tissue biopsies, confocal endomicroscopies, and blood, stool, urine, and breath tests (Lawson, 2024; Jones, 2025).

Works Cited:

1.     Anatomy and Physiology 2e. (2022). OpenStax.

2.     Camilleri, M., & Vella, A. (2022). What to do about the leaky gut. Author Manuscript, 71(2), 424–435. 10.1136/gutjnl-2021-325428.

3.     Di Vincenzo, F., Del Gaudio, A., Petito, V., Lopetuso, L. R., & Scaldaferri, F. (2024). Gut microbiota, intestinal permeability, and systemic inflammation: A narrative review. Springer, 19, 275-293. 10.1007/s11739-023-03374-w

4.     Jones, P. (2025, March 4). Leaky gut syndrome. Zoe. https://zoe.com/learn/what-is-leaky-gut

5.     Lawson, F. (2024, March 4). Testing for leaky gut syndrome – the complete guide. Health Path. https://healthpath.com/leaky-gut/testing-leaky-gut-syndrome-complete-guide/

6.     “Leaky Gut Syndrome.” (n.d.). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22724-leaky-gut-syndrome

7.     Lipski, E. (2013). Digestion connection: The simple, natural plan to combat diabetes, heart disease, osteoporosis, arthritis, acid reflux – and more! Rodale.

8.     Sicard, J.-F., Le Bihan, G., Vogeleer, P., Jacques, M., & Harel, J. (2017). Interactions of intestinal bacteria with components of the intestinal mucus. Frontiers in Cellular and Infection Microbiology, 7, 1-12. 10.3389/fcimb.2017.00387

9.     “11 Symptoms and Causes of Leaky Gut Syndrome.” (2019). Medanta. https://www.medanta.org/patient-education-blog/11-signs-you-have-the-leaky-gut-and-how-to-heal-it