Biomarkers for Leaky Gut
Content
1. What is Leaky Gut
2. Biomarkers for Leaky Gut
2.1 Zonulin
2.2 Alpha-1-antitrypsin
2.3 Secretory IgA (sIgA)
2.4 I-FABP
2.5 Calprotectin
3. Significance of the biomarkers
1. What is Leaky Gut
The so-called “Leaky Gut Syndrome” is gaining increasing attention. It refers to an increased permeability of the intestinal lining, allowing unwanted substances such as bacteria, toxins, or undigested food particles to enter the bloodstream. This condition, known as intestinal hyperpermeability, has been linked to various symptoms and chronic conditions, including food intolerances, autoimmune diseases, and inflammatory processes (1).
2. Biomarkers for Leaky Gut
Leaky Gut Syndrome is a not recognized medical diagnosis in conventional medicine (as of June 2025), which is why there is no standard diagnostic test for leaky gut. Nevertheless, there are specialized laboratory markers that can provide indications of a compromised intestinal barrier.
2.1 Zonulin
Zonulin is currently one of the most frequently studied markers in connection with leaky gut. Zonulin is a protein that regulates the permeability of tight junctions, which are the cell connections in the intestine. Zonulin can loosen these “seals” between the cells of the intestinal lining, thereby increasing the permeability of the intestinal wall. An elevated zonulin level in stool or blood can be an indication of a compromised intestinal barrier. Testing for zonulin levels can be a good initial approach for diagnosing leaky gut (2).
2.2 Alpha-1-antitrypsin
Alpha-1-antitrypsin is a marker that can be measured in stool and may indicate inflammatory processes and protein loss in the intestine. Alpha-1-antitrypsin is primarily produced in the liver and serves to regulate inflammatory processes. Elevated levels of alpha-1-antitrypsin suggest a loss of this protein through the intestinal wall into the gut, indicating increased intestinal permeability or mucosal inflammation (3).
2.3 Secretory IgA (sIgA)
Secretory immunoglobulin A (sIgA) is part of the gut-associated immune system. Immunoglobulins are antibodies, which are proteins produced by the immune system to defend against pathogens. Secretory IgA can be measured in stool as well. Elevated levels of sIgA in stool may indicate an acute immune response (4). This inflammatory process is often associated with increased intestinal permeability.
2.4 I-FABP
I-FABP stands for intestinal fatty acid-binding protein. It is located in the cytoplasm of intestinal epithelial cells and helps with the absorption of fatty acids from the intestinal lumen. When the intestinal cells are damaged, I-FABP is released into the bloodstream. An increase in I-FABP levels in the serum can therefore indicate acute intestinal damage or disruption of the intestinal epithelium, and thus increased permeability of the intestinal wall (5).
2.5 Calprotectin
Calprotectin, when measured in stool, is an inflammatory marker for the intestine (6). The protein calprotectin is primarily found in neutrophil granulocytes (a type of white blood cell). These immune cells play a central role in inflammatory responses in the body. When inflammation occurs in the intestine, neutrophil granulocytes migrate into the intestinal lining in increased numbers. During this process, calprotectin is released and passes into the stool, where it can be measured.
3. Significance of the biomarkers
Interpreting laboratory values requires experience, as individual results are rarely definitive. A comprehensive diagnosis should always be made in the context of symptoms, medical history, and possibly additional tests such as microbiome analysis. Although conventional medicine has not yet officially recognized the term “leaky gut,” many patients show significant improvement in their symptoms through targeted therapeutic approaches based on such laboratory findings.
References
- Leech B, McIntyre E, Steel A, Sibbritt D. Risk factors associated with intestinal permeability in an adult population: A systematic review. Int J Clin Pract. 2019 Oct;73(10):e13385. doi: 10.1111/ijcp.13385 Titel anhand dieser DOI in Citavi-Projekt übernehmen. Epub 2019 Jul 5. PMID: 31243854
- Wegh CAM, de Roos NM, Hovenier R, Meijerink J, Besseling-van der Vaart I, van Hemert S, Witteman BJM. Intestinal Permeability Measured by Urinary Sucrose Excretion Correlates with Serum Zonulin and Faecal Calprotectin Concentrations in UC Patients in Remission. J Nutr Metab. 2019 Apr 1;2019:2472754. doi: 10.1155/2019/2472754
- Strygler B, Nicar MJ, Santangelo WC, Porter JL, Fordtran JS. Alpha 1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. Gastroenterology. 1990 Nov;99(5):1380-7. doi: 10.1016/0016-5085(90)91165-3. PMID: 2210245.
- Li Y, Jin L, Chen T. The Effects of Secretory IgA in the Mucosal Immune System. Biomed Res Int. 2020 Jan 3;2020:2032057. doi: 10.1155/2020/2032057. PMID: 31998782; PMCID: PMC6970489.
- Funaoka H, Kanda T, Fujii H. [Intestinal fatty acid-binding protein (I-FABP) as a new biomarker for intestinal diseases]. Rinsho Byori. 2010 Feb;58(2):162-8. Japanese. PMID: 20229815.
- Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2015 Jun;110(6):802-19; quiz 820. doi: 10.1038/ajg.2015.120. Epub 2015 May 12. PMID: 25964225.
