Intestinal permeability: Everything you need to know about the root of many diseases.

Intestinal permeability  refers to the property of the membranes of the intestinal tract in allowing the passage of different macromolecules. 

It is a complex system consisting of an external “physical” barrier and an internal “functional” barrier (immune barrier). 

This immune barrier is made up of the intestinal mucosa, which aims to allow symbiosis (a beneficial association between two organisms) without developing a condition of chronic inflammation and response to the threat of pathogens. 

The interaction of physical and immunological barriers allows to maintain the intestinal permeability balance. 

The intestinal epithelium is generally effective against the passage of macromolecules, bacterial products and food antigens; however, a small percentage can pass through the tight junctions. 

In individuals with a genetic predisposition, the passage of luminous materials may be related to an exaggerated immune activation and to the release of cytokines, such as IL-13, TNF, and IFN-y. As a result, increased permeability of the tight junctions can lead to additional passage of macromolecules from the intestinal lumen and increased immune activation. 

The lack of an adequate regulation and the increase of these cytokines can cause several diseases, as we will see below. 

What is intestinal permeability? 

Intestinal permeability is, therefore, the functional characteristic of the intestinal barrier, which can be measured by analyzing the flow rates along the intestinal wall as a whole or by inert substances during the absorption process. 

It is most commonly measured by fractional urinary excretion of probes taken orally. These probes can pass through the intestinal epithelium via the paracellular route and enter bloodstream. Thus, the probes are filtered through the glomerulus and excreted in the urine. 

The ideal probes are not metabolized in the intestinal lumen or in the blood, are easily filtered by the glomerulus and are not actively absorbed or secreted in the kidney. Fractional urinary excretion can, therefore, be used as an indirect measure of intestinal permeability. 

Thus, a normal intestinal permeability is defined as a stable permeability found in healthy individuals without signs of intoxication, inflammation or impaired intestinal functions. 

What are the causes of the change in intestinal permeability? 

Many factors can modify intestinal permeability: 

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

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

The effect of diet on intestinal permeability depends on individual factors, such as the individual’s genetic susceptibility, as well as his or her intestinal microbiota. 

Dietary factors can promote an increase in intestinal permeability as a result of changes in intestinal microbiota, such as during metabolic adaptation to a high-fat diet (HFD). 

Vitamin A 

A vitamin A deficient diet can cause changes in commensal bacteria and damage the intestinal barrier, changing the dynamics of mucin and the expression of defense molecules. 

Studies with children with subclinical vitamin A deficiency have shown that serum retinol concentrations are inversely correlated with intestinal permeability. 

Vitamin D 

In addition to vitamin A, vitamin D also appears to play an important role in intestinal barrier. Experiments in mice have shown that vitamin D deficiency can compromise the mucosal barrier, leading to an increased susceptibility to mucosal damage and an increased risk of intestinal barrier diseases. 

Short-chain fatty acids 

These organic acids include acetate, propionate, butyrate and valerate, which are produced by intestinal microbial fermentation of undigested carbohydrates in the colon. Among them, butyrate plays an important role in maintaining the intestinal barrier, in which its deficiency causes lesions in the tight junction, altering intestinal permeability. 

Western-style diets 

High-energy, high-fat diets increased intestinal permeability, resulting in metabolic endotoxemia (altered permeability due to LPS, a component of the outer membrane of gram-negative bacteria). 

Prebiotics 

In addition to the effects of the fermentation products of prebiotics such as short-chain fatty acids, prebiotics can stabilize the intestinal barrier. A recent study showed that fructooligosaccharides (FOS) attenuates liver steatosis, possibly modulating the intestinal microbiota and/or the intestinal barrier function. 

Probiotics   

Several studies demonstrate the use of commensal bacteria and probiotics to promote the integrity of the intestinal barrier in vivo. 

Intestinal dysbiosis (imbalance of intestinal bacterial flora) has been shown to lead to intestinal barrier dysfunction and modulation, as well as chronic disease states, such as irritable bowel syndrome.  

The change in intestinal permeability and subsequent translocation of bacteria can trigger several metabolic diseases. 

It is speculated that the adjustment of the intestinal microbiota, with prebiotic foods or probiotic bacteria, may help in future therapies for diseases related to the intestinal barrier. 

What are the main clinical changes and effects of intestinal permeability? 

The increase in intestinal permeability is present in several systemic and intestinal clinical conditions: 

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

Effects of increased intestinal permeability include: 

• Increase in antigens that can trigger food allergy (IgE), food intolerance (IgG), inflammatory and autoimmune diseases.
• High exposure to toxins due to the overload of the liver’s detoxification function and “fatigue” due to the high consumption of ATP.
• High exposure to pathogens, caused by an increase in antigens and bacterial products.

On the other hand, the decrease in intestinal permeability can result in malabsorption and cause malnutrition, even with a normal diet (in terms of quality or quantity), commonly as a consequence of lesions of the intestinal epithelium that affect the transcellular absorption of nutrients. 

What is the intestinal permeability test or IP test? 

It is a non-invasive method of assessing the integrity and functionality of the intestinal mucosa, which allows for assistance in diagnosing the causes of intestinal and systemic symptoms, in addition to providing information on the therapeutic response and clinical follow-up (activity and prognosis marker). 

The analysis consists of the administration of two non-metabolizable substances (lactulose and mannitol) that have different molecular weight, in previously determined 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 perform the test, 8 hours of fasting is required. 

• When waking up, one must urinate, thus emptying the bladder completely.
• Afterwards, dilute mannitol and lactulose according to the instructions and ingest slowly.
• Food and liquids should not be consumed within the first hour of the procedure.
• Urinate in the graduated bottle for 6 hours and keep the bottle stored in the refrigerator during and after collection, until sent to the laboratory.
• After collection, mix the graduated flask and transfer 10 mL of urine to the collection probe.
• Discard the waste from the collection vial
• Submit the 10 mL of urine properly identified and stored to the laboratory, following the instructions provided.

Who is the intestinal permeability test indicated to? 

The intestinal permeability test is indicated to: 

• People who want to proactively manage their health;
• People who have any food allergies and/or intolerance;
• Patients with celiac disease or gluten intolerance;
• Patients with chronic intestinal diseases or symptoms;
• Patients with chronic inflammatory or immune systemic diseases.

The identification of a change in intestinal permeability allows therapeutic action in a specific way, with the consequent improvement of symptoms in a high percentage of patients. 

About the SYNLAB Group 

The SYNLAB Group is a leader in providing medical diagnostic services in Europe, providing a full range of clinical laboratory analysis services to patients, healthcare professionals, clinics and the pharmaceutical industry. Resulting from the Labco and Synlab merger, the new SYNLAB Group is the undisputed European leader in medical laboratory services.