Intestinal Permeability: Everything You Need to Know About the Root of Many Diseases

Intestinal permeability is a characteristic of the membranes of the intestinal tract that allows the controlled passage of different macromolecules (1). 

This intestinal barrier consists of two integrated systems: an external physical barrier and an internal functional barrier, which includes the immune barrier. 

The immune barrier, formed by the intestinal mucosa, works to maintain a beneficial symbiosis between the organism and intestinal microorganisms, preventing chronic inflammation and excessive responses to pathogens. 

The interaction between the physical and immune barriers contributes to the proper balance of intestinal permeability. In general, the intestinal epithelium blocks the passage of macromolecules, bacterial products, and food antigens, allowing only a small amount to pass through tight junctions. 

However, in genetically predisposed individuals, the passage of substances through the epithelium can trigger an exaggerated immune response, releasing cytokines such as IL-13, TNF, and IFN-γ. This increase in permeability of tight junctions facilitates the passage of more macromolecules from the intestinal lumen, promoting even greater immune activation (2). 

Insufficient regulation of this response and increased cytokines may be associated with various diseases, as we will see next. 

What is Intestinal Permeability?  

Intestinal permeability refers to the functional capacity of the intestinal barrier, which can be measured by analyses of the flow rate along the intestinal wall or through the absorption of inert substances. 

Commonly, permeability is assessed by the urinary excretion of inert probes ingested orally. These probes cross the epithelium via the paracellular pathway, enter the bloodstream, are filtered by the glomerulus, and then excreted in the urine. 

The ideal probes for this assessment should not be metabolized in the intestinal lumen or in the blood, should be easily filtered by the kidneys, and should not be absorbed or actively secreted by the renal tubules. Thus, the fractional urinary excretion of the probes serves as an indirect measure of intestinal permeability. 

Therefore, normal intestinal permeability is defined as that which occurs in healthy individuals, without signs of inflammation, intoxication, or impairment of intestinal function. 

What Are the Causes of Altered Intestinal Permeability?  

Various factors can alter intestinal permeability, such as: 

• Modifications in the intestinal microbiota;
• Changes in the mucosal layer;
• Epithelial damage, which results in the translocation of luminal content to the inner layers of the intestinal wall;
• Lifestyle and dietary factors, such as alcohol consumption and energy-rich diets, such as the Western diet, which has a high caloric value.

What are the effects of diet, prebiotics, and probiotics on intestinal permeability? 

The effects of diet on intestinal permeability vary according to individual factors, such as the individual’s genetic susceptibility and the composition of the intestinal microbiota (3). 

Certain dietary components can increase intestinal permeability by modulating the microbiota. For example, high-fat diets (HFD) can promote metabolic changes that affect the function of the intestinal barrier (4). 

Vitamin A 

A diet low in vitamin A can cause changes in commensal bacteria, compromising the intestinal barrier and altering mucin production and the expression of defense molecules (5). 

Studies with children with subclinical vitamin A deficiency have shown that lower serum retinol levels are inversely correlated with intestinal permeability (6). 

Vitamin D 

Vitamin D also plays an important role in maintaining intestinal barrier health. Studies in mice have shown that vitamin D deficiency can weaken the intestinal mucosa, increasing susceptibility to damage and raising the risk of intestinal diseases (7). 

Short-Chain Fatty Acids 

These organic acids include acetate, propionate, butyrate, and valerate, which are produced by microbial fermentation of undigested carbohydrates in the colon. Butyrate, in particular, is crucial for maintaining the intestinal barrier, as its deficiency causes damage to tight junctions, increasing intestinal permeability (8). 

Western Diets 

Typical Western diets, rich in energy and fat, have been associated with increased intestinal permeability, leading to metabolic endotoxemia, a condition caused by the absorption of LPS, a component of the membrane of Gram-negative bacteria (9). 

Prebiotics 

In addition to producing short-chain fatty acids through fermentation, prebiotics help stabilize the intestinal barrier. A recent study showed that fructooligosaccharides (FOS) can reduce hepatic steatosis, possibly by modulating the intestinal microbiota and the function of the intestinal barrier (10). 

Probiotics 

Studies indicate that the use of commensal bacteria and probiotics may promote the integrity of the intestinal barrier in vivo. 

It has been shown that intestinal dysbiosis (imbalance of the intestinal microbiota) can compromise the intestinal barrier, leading to dysfunctions and chronic diseases, such as in irritable bowel syndrome (11). One of the ways to analyze the microorganisms that make up the gut ecosystem is through complete microbial genome sequencing (shotgun metagenomics) in the MyBiome test. 

Alterations in intestinal permeability and the translocation of bacteria out of the intestine can trigger metabolic diseases. Thus, it is believed that adjustments in the microbiota through prebiotic or probiotic foods may be a promising therapeutic approach for diseases related to the intestinal barrier (12). Here on our blog, we have already discussed the importance of gut microbiota for maintaining health. 

What Are the Main Clinical Changes and Effects of Intestinal Permeability?  

Increased intestinal permeability is present in various clinical intestinal and systemic conditions, such as: (13) 

• Food allergy;
• Food intolerance;
• Celiac disease;
• Crohn’s disease;
• Rheumatoid arthritis;
• Ankylosing spondylitis;
• Type 1 diabetes;
• Multiple sclerosis;
• Chronic dermatological diseases.

The effects of increased intestinal permeability include: 

• Increased antigens potentially triggering food allergy (IgE), food intolerance (IgG), inflammatory and autoimmune diseases (understand the differences between allergy and intolerance here on the blog);
• Increased exposure to toxins due to overload of the liver detoxification function and “fatigue” from high ATP consumption;
• Increased exposure to pathogenic agents caused by the rise in antigens and bacterial products.

Conversely, decreased intestinal permeability can result in malabsorption and malnutrition, even with a normal diet (in terms of quality or quantity), commonly as a consequence of epithelial damage affecting the transcellular absorption of nutrients. 

How is the Intestinal Permeability Test or SYNLAB PI Test?  

The intestinal permeability test is a non-invasive method for assessing the integrity and functionality of the intestinal mucosa. It helps diagnose the causes of intestinal and systemic symptoms, providing information on therapeutic response and clinical monitoring (activity marker and prognosis). 

The analysis consists of administering two non-metabolizable substances (lactulose and mannitol) that have different molecular weights, at predetermined concentrations. The result is presented based on the quantification of the percentage of elimination of both substances, which is correlated with the percentage of absorption. 

How to Perform the Intestinal Permeability Test? 

To conduct the test, an 8-hour fasting period is required. 

• Upon waking, urinate to completely empty the bladder.
• Next, dilute the mannitol and lactulose according to the instructions and ingest them slowly.
• Do not consume any food or liquids during the first hour of the procedure.
• Urinate in the graduated container over a period of 6 hours, and keep the container refrigerated during and after the collection until it is sent to the laboratory.
• After the collection, homogenize the graduated container and transfer 10 mL of urine to the collection tube.
• Discard the residual urine from the collection container.
• Send the 10 mL of urine to the laboratory, properly labeled and packaged, following the provided instructions.

Who is the Intestinal Permeability Test Indicated For?  

The intestinal permeability test is indicated for: 

• Individuals wishing to proactively manage their health;
• Individuals with any food allergies and/or intolerances;
• Patients with celiac disease or gluten intolerance;
• Patients with chronic intestinal diseases or symptoms;
• Patients with chronic inflammatory or immunological systemic diseases.

Identifying a change in intestinal permeability allows for specific therapeutic intervention, resulting in significant symptom improvement in a high percentage of patients. 

Discover the SYNLAB Group, a reference in medical diagnostic services!  

Performing accurate and up-to-date tests is essential for more precise diagnoses and better treatment direction. SYNLAB is here to help you. 

We offer diagnostic solutions with strict quality control to the companies, patients, and physicians we serve. We have been in Brazil for over 10 years, operate in 36 countries across three continents, and are leaders in providing services in Europe. 

Contact the SYNLAB team to learn about the available tests. 

References 

(1) Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol. 2013 Sep;11(9):1075-83. doi: 10.1016/j.cgh.2013.07.001.

(2) Clayburgh DR, Barrett TA, Tang Y, Meddings JB, Van Eldik LJ, Watterson DM, Clarke LL, et al. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest. 2005 Oct;115(10):2702-15.

(3) Moreira APB, Texeira TFS, Ferreira AB, Peluzio MCG, Alfenas RCG. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr. 2012 Sep;108(5):801-9.

(4) Serino M, Luche E, Gres S, Baylac A, Bergé M, Cenac C, Waget A. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut. 2012:61(4):543-53.

(5) Amit-Romach E, Uni Z, Cheled S, Berkovich Z, Reifen R. Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet. J Nutr Biochem. 2009 Jan;20(1):70-7.

(6) Lima AM, Soares AM, Lima NL, Mota RMS, Maciel BLL, Kvalsund MP, et al. Effects of vitamin A supplementation on intestinal barrier function, growth, total parasitic, and specific Giardia spp infections in Brazilian children: a prospective randomized, double-blind, placebo-controlled trial. J Pediatr Gastroenterol Nutr. 2010 Mar;50(3):309-15.

(7) Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16.

(8) Plöger S, Stumpff F, Penner GB, Schulzke JD, Gäbel G, Martens H, et al. Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann N Y Acad Sci. 2012 Jul:1258:52-9.

(9) Pendyala S, Walker JM, Holt PR. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology. 2012 May;142(5):1100-1101.e2.

(10) Pachikian BD, Essaghir A, Demoulin JB, Catry E, Neyrinck AM, et al. Prebiotic approach alleviates hepatic steatosis: implication of fatty acid oxidative and cholesterol synthesis pathways. Mol Nutr Food Res. 2013 Feb;57(2):347-59.

(11) Rosenfeldt V, Benfeldt E, Valerius NH, Paerregaard A, Michaelsen KF. Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatites. J Pediatr. 2004 Nov;145(5):612-6.

(12) Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol. 2014 Nov 18;14:189.

(13) Odenwald MA, Turner JR. Intestinal permeability defects: is it time to treat? Clin Gastroenterol Hepatol. 2013 Sep;11(9):1075-83.