Leaky gut – does it really exist?

Symptoms of Leaky gut syndrome accompany almost all diseases of the digestive tract. Instead, it is not known whether it is the cause of their occurrence, or, on the contrary, develops as a result of these diseases. Also, treatment methods and their effectiveness are still discussed, while this syndrome is widespread and leads to a big list of different serious diseases. So, let’s find out what is Leaky gut syndrome and how to protect yourself from it.

What is this syndrome and how widespread is it today?

“Leaky gut” is a simplified term for increased intestinal permeability (IP). This problem is actually attracting more and more attention from both scientists and clinicians around the world today. However, despite the progressive increase in the number of scientific data about this syndrome, there are many myths surrounding “leaky gut” and its role in the development of other non-infectious diseases (1).

Information on the prevalence of leaky gut syndrome in the general population is not sufficient. However, it was established that it increases with:

To understand the factors of development and clinical manifestation of the leaky gut syndrome, it is worth recalling the functions of the intestinal barrier and its structure. The intestinal barrier prevents pathogenic microorganisms and toxic factors from entering the body while regulating the absorption of nutrients, electrolytes, and water.

The implementation of these functions of the intestinal barrier is facilitated by its complex multi-layered structure, represented by external physical and internal functional immunological barriers (1).

The development of the “leaky gut” condition is influenced by:

Certain nutrients can also alter intestinal permeability, thereby influencing the immune response without involving the microbiota.

In contrast, other dietary compounds prevalent in the Western diet disrupt the integrity of the gut barrier by altering the expression and distribution of proteins and promoting the translocation of pathogenic or opportunistic bacteria.

A leaky gut is a start point for many diseases

Increased intestinal permeability is the pathophysiological basis of several diseases. For example, food allergy can be associated with this syndrome. In the study conducted, children with food allergies were found to have increased intestinal permeability (IP) (1). It was observed in approximately one-third of children with food allergies: clinical symptoms disappeared against the background of the use of elimination diets. Elevated IP was also associated with short stature in these children.

According to many authors, the development of rheumatoid arthritis is associated with disturbances in the composition of the intestinal microbiota: the excessive proliferation of Prevotella species, which contribute to the development of an inflammatory reaction, inducing IL-6 and IL-23 cytokines and increasing intestinal permeability (2). In addition, high levels of Prevotella and similar species correlate with reduced numbers of protective microbiota, which are thought to regulate the immune response. Therefore, an increase in intestinal permeability against the background of an increase in the number of microorganisms of the genus Prevotella in the early stages of rheumatoid arthritis can probably become an important pathophysiological mechanism of its development.

Other common autoimmune diseases in which the pathogenetic role of elevated IP has been studied include type 1 diabetes (T1DM) and systemic lupus erythematosus. For example, studies have shown that in T1 diabetes, the intestinal barrier function is impaired before the disease manifests itself (3). And the restoration of the intestinal barrier contributed to the improvement of the course of T1DM in animals, which potentially indicates a significant role of the “leaky gut” in the progression of T1DM. It has also been confirmed that the development and progression of systemic lupus erythematosus are associated with lipopolysaccharide stimulation and TLR4 activation. Conversely, inhibition of TLR4 leads to a decrease in the production of autoantibodies (4).

During the examination of patients with chronic fatigue syndrome, it was found that the content of serum IgA against lipopolysaccharides of enterobacteria was significantly higher in them than in healthy volunteers.

A number of studies point to the contribution of the microbiota to the maintenance of physical barriers, such as the blood-brain barrier (BBB) or intestinal barrier, by influencing tight junctions between cells (5). Similarly, bile acids can activate receptors in the host body and act as signalling particles, as well as affect barrier permeability (6). In addition, lipopolysaccharide (LPS), produced by bacteria, can affect BBB permeability, causing the release of inflammatory cytokines (7). Moreover, serum IgA levels were significantly correlated with disease severity and symptoms such as irritable bowel, muscle tension, fatigue, difficulty concentrating, and memory impairment. This gave reason to assume that enterobacteria are one of the etiological factors of the disease, and elevated IP mediates the formation of an immune response to gram-negative enterobacteria. Even the idea of ​​examining all patients with chronic fatigue syndrome with the help of an IgA panel and carrying out appropriate treatment was expressed.

Neurotransmitters and their precursors produced in the gut can also affect their levels in the brain. In addition to being obtained from the breakdown of food, neurotransmitters can also be produced by bacteria. For example, Escherichia coli can release dopamine, serotonin, and norepinephrine, while Lactobacilli produce serotonin, GABA, acetylcholine, and histamine (8), which can affect the host brain. This mechanism plays an important role in the development of several neurological diseases, including Alzheimer’s disease, Parkinson’s disease (PD), depressive disorders, and autism spectrum disorders (9; 10). In addition, SCFAs can indirectly influence the gut-brain axis by inducing the release of certain gut hormones, such as glucagon-like peptide-1 (GLP-1) and leptin, via enteroendocrine cells. These intestinal hormones can interact with the vagus nerve and even brain receptors (11). Accordingly, as a result of violations of the microbiota as a result of increased permeability of the intestinal walls, a cascade of a wide variety of diseases is launched.

Leaky gut syndrome symptoms and diagnostic’ methods

Clinically, the syndrome is manifested by such symptoms as:

The methods of diagnosing leaky gut syndrome can be divided into two groups (1):

Most often, IP is measured indirectly due to the determination of partial urinary excretion of orally administered molecular probes that cross the intestinal epithelium by a paracellular route, enter the blood, are filtered by the glomerulus, and are excreted in the urine without active reabsorption in the kidneys. At the same time, the fractional excretion of these substances can be used as an indirect indicator of intestinal permeability.

The most frequently used molecular probes include saccharides (sucralose, mannitol, lactulose, etc.). It should be noted that each molecular probe has its own absorption characteristics. So, sucrose is informative only in the first hour after consumption, because it is quickly metabolized to glucose and fructose, and therefore, in the best case, provides information about the permeability of the stomach and duodenum (1).

Other monosaccharides (mannitol, rhamnose) and disaccharides (lactulose, sucralose) are absorbed in the small and large intestine, and the time of urinary excretion provides the best way to differentiate the localization of pathological abnormalities. However, despite certain achievements in the development of these methods, they still remain insufficiently valid and require additional research (1).

In addition, methods of detecting serological (zonulin, claudin-3, lipopolysaccharides, etc.) and coprological markers (calprotectin, zonulin, etc.) are also used. At the same time, the effectiveness and validity of the specified methods still require proof and further research.

Recently, a new method of diagnosing leaky gut was invented – the so-called PANDA (Platelet Number in Different Anticoagulants) test, invented by Prof. Dr. Goetz Nowak, Erfurt, Jena – Germany. It is based on the LPS loading measure as a marker of hidden intestine inflammation in the organism. The main principle of this laboratory test is to compare the difference in the number of platelets in heparin-diluted and in “normal” EDTA-diluted blood (12). If it is less than 10% – everything is ok. But if the difference between the two samples is more than 10 % – a patient has got high intestinal permeability and may be low-grade inflammation. PANDA test can be used for screening LPS-loaded platelets as an indirect diagnostic biomarker for increased intestinal permeability and for monitoring the gut barrier function during the treatment of gastrointestinal diseases. By the way, the PANDA test is one of the most economical intestinal barrier test procedures with only two small blood samples, automatically counted and compared.

Prevention and treatment

In order to prevent or at least postpone disease, that could develop further from leaky gut, it is good to know if you have it and start treating it as soon as possible. Early treatment of leaky gut can prevent further, much more complicated health issues.

According to modern ideas, the functional state of the intestinal barrier can be influenced in two ways:

This way, taking special supplements is crucial for healing Leaky gut syndrome. We recommend using a perfect combination of Neotosil®, Multi EM ferment®, and Premium Asta O3® supplements. These supplements consist of special bacteria and nutrients that help restore barrier function like vitamins A and E, omega 3 acids, and others. Later in the article, we highlighted the special benefits of the combination of these supplements and some of their components for the health of the intestines and the whole body.

For example, Vitamin A and its derivatives regulate the growth and differentiation of intestinal cells (13). The deficiency of this vitamin is associated with increased susceptibility to infectious lesions. Thus, a diet deficient in vitamin A within a few weeks leads to a change in the composition of the intestinal microbiota and impairs the intestinal barrier, disrupting mucin dynamics and the expression of protective molecules such as MUC2 and defensin-6.

Vitamin E has many benefit functions (14). It acts as an antioxidant. This means it protects body tissue from damage caused by substances called free radicals. Free radicals can harm cells, tissues, and organs. They are believed to play a role in certain conditions related to ageing. The body also needs vitamin E to help keep the immune system strong against viruses and bacteria. Vitamin E is also important in the formation of red blood cells. It helps the body use vitamin K. It also helps widen blood vessels and keep blood from clotting inside them. Cells use vitamin E to interact with each other. It helps them carry out many important functions. Also, there is research that vitamin E can prevent cancer, heart disease, dementia, liver disease, and stroke. Vitamin E also plays a significant role in maintaining the intestinal barrier, which may be associated with its antioxidant activity.

Omega 3 fatty acids are very important, as they can reduce intestinal permeability, and can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages (15). Also, a new study finds that people who eat foods rich in omega-3 fatty acids have more bacterial diversity in the gut, which promotes better overall health (16). This way, pure and high-quality EPA and DHA in Premium Asta O3® are crucial in maintaining gut health.

β-Glucans play a special role in maintaining the intestinal barrier (17). They are naturally occurring polysaccharides that are produced by bacteria, yeast, fungi, and many plants. Their pharmacological activities, such as immunomodulatory, anti-infective, and anti-cancer effects, have been well studied. β-Glucan has been shown to protect against infection by bacteria, viruses, and pathogenic microorganisms (17). β-Glucan also prevents cancer promotion and progression and has synergistic anti-tumour effects with monoclonal antibodies and cancer chemotherapeutics. Traditionally macrophages and dendritic cells are considered the main target cells of β-glucans, although neutrophils, B cells, T cells, and natural killer cells are also known to be activated by β-glucan.

Several studies confirm the effectiveness of probiotics in restoring the functional state of the intestinal barrier (18). They are known for their ability to protect and restore intestinal permeability in vitro and in vivo. The multi-strain probiotics are more efficient than that a single strain in terms of their protective efficacy. These probiotic strains include Enterococcus faecium, different Bifidobacteria, Lactobacilli, and many others. They showed a positive effect on kidney and liver function, lipid profile, intestinal integrity, microbial metabolites, bacterial endotoxin (LPS) level, and biomarkers of gut-brain communication pathways. The results revealed that the supplementation of studied probiotics improved the intestinal barrier function, lipid profile, and obesity-related biomarkers in human subjects.

And finally, intestinal pathogens often gain access to the body by changing the structure and functional state of tight junctions, increasing the permeability of the intestinal barrier by secreting proteases that can cleave the proteins of these junctions and alter the cytoskeleton. Therefore, the use of various flavonoids and polyphenols that are combined in Neotosil® and Multi EM ferment®, and antioxidant Astaxanthin from Premium Asta O3® which have pronounced antimicrobial, anti-inflammatory, and antioxidant effects, can be a promising direction in the restoration of the intestinal barrier. In addition, inflammatory cytokines such as TNFα and IFNγ, which are synthesized in infectious lesions and inflammatory bowel diseases, also increase its permeability, while probiotics and polyphenols can eliminate inflammatory changes in the intestinal epithelium, thereby improving barrier function and inhibiting the adhesion of pathogens.

For example, Quercetin is most commonly used for conditions of the heart and blood vessels and to prevent cancer (19). It is also used for arthritis, bladder infections, and diabetes. Previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels.  Also, it is effective in various disease conditions connected with oxidative stress, such as cancer, Alzheimer’s, renal diseases, cardiac abnormalities, etc. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities.

Resveratrol is a natural compound found in red grape skin, Japanese knotweed, peanuts, blueberries, and some other berries. It is a powerful antioxidant produced by some plants to protect them against environmental stresses (20). Resveratrol protects a cell’s DNA. It is a powerful antioxidant and helps to prevent cell damage caused by free radicals (cancer, ageing, brain degeneration, ageing). Resveratrol has been promoted to have many health benefits such as protecting the heart and circulatory system, lowering cholesterol, and protecting against clots that can cause heart attacks and stroke. Animal studies have suggested it can lower blood sugar levels. Because resveratrol is considered an antioxidant, it is often promoted to reduce the incidence of various cancers. Animal studies also suggest resveratrol may lower brain plaque levels in Alzheimer’s disease.

Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric. Curcumin is a naturally occurring yellow pigment of turmeric having a wide spectrum of biological action (21). Curcumin has been used extensively in ayurvedic medicine for centuries, as it is non-toxic and has a variety of therapeutic properties including antioxidant, analgesic, anti-inflammatory, antiseptic activity, anticarcinogenic activity, chemopreventive, chemotherapeutic activity, anti-tumour, antiviral, antibacterial, antifungal properties and antiplatelet activity (22). Curcumin exhibits a big promise as a therapeutic agent due to its properties and is currently in human trials for a variety of conditions like multiple myeloma, pancreatic cancer, colon cancer, mastitis myelodysplastic syndromes, psoriasis, Alzheimer’s disease, diabetic nephropathy, periodontal disease, oral cancers, recurrent aphthous stomatitis, precancerous lesion, and conditions, etc (23).

Conclusion

Treating Leaky gut syndrome is a very difficult task since there is no clear etiology, and insufficiently developed diagnostics and the syndrome can affect all tissues and organs of the body at the cellular level. It is not for nothing that it is called a “therapeutic nightmare”. Thus, the most correct approach to treatment will be to restore the deep needs and protective capabilities of the body itself thanks to beneficial bacteria, nutrients, and polyphenols, for example, taking Neotosil®, Multi EM ferment®, and Premium Asta O3® supplements. The combination of strains of beneficial bacteria selected by experts, effective polyphenols from selected plants and fruits, in combination with vitamins and other nutrients proved to be beneficial for regulating health problems that have developed based on gut imbalance (dysbiosis and intestinal permeability). Numerous studies confirm their remarkable properties, in particular anti-inflammatory and antioxidant strengths. They have the most powerful formulas with bacteria strains, polyphenols, provitamins, and vitamins with the highest bioavailability and effectiveness that is perfect for Leaky gut syndrome treatment and different chronic diseases developed from inflammation due to damage to the gastrointestinal mucosa: cardiovascular disease, diabetes, metabolic syndrome, cancer, multiple sclerosis, Parkinson’s disease, Alzheimer’s dementia, autism, ADHD, celiac disease, rheumatoid arthritis, etc; and are safe even for kids and pregnant women.

References

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