Leaky Gut Syndrome: Causes and Treatment
Content
1. What is leaky gut?
1.1 Symptoms of leaky gut
1.2 Diagnostic Approaches for Leaky Gut
2. Causes of Leaky Gut Syndrome
2.1 Diet
2.2 Infections
2.3 Exogenous factors
2.4 Lifestyle and Stress
3. Therapy
3.1 Diet & Lifestyle
3.2 Supplements
4. Summary
1. What is leaky gut?
Leaky gut syndrome describes a condition in which the intestinal mucosa (gut lining) becomes more permeable, referred to as “increased intestinal permeability.” Leaky gut is often associated with activation of the immune system (inflammatory responses) and a disrupted gut microbiome.
The human intestinal mucosa consists of three main layers: The innermost layer, facing the lumen (the inside of the intestine), is a mucus layer that serves to protect intestinal cells (enterocytes). Enterocytes, together with other specialized intestinal cells, form a single-cell layer that separates the intestinal interior from the body and bloodstream. Beneath the enterocytes is a layer filled with immune cells.
Enterocytes play a crucial role in protecting the body from harmful substances or pathogens while simultaneously absorbing essential nutrients from food. To perform these functions effectively, enterocytes are tightly connected by structures known as tight junctions. If these connections loosen, making the intestine more permeable, the condition is referred to as leaky gut syndrome.
1.1 Symptoms of leaky gut
Leaky gut is primarily associated with symptoms such as diarrhea, constipation, bloating and gas, abdominal pain and discomfort, as well as fatigue, headaches, muscle pain, and difficulty concentrating (“brain fog”). Skin issues like acne, eczema, and rosacea, along with joint pain and systemic inflammation, are also possible symptoms.
Conditions associated with leaky gut also include psychological symptoms such as depression and anxiety, chronic fatigue, autoimmune diseases (e.g., rheumatoid arthritis, psoriasis), and diabetes (1).
Since the 1970s, leaky gut syndrome has been recognized in connection with intestinal inflammation, chronic inflammatory bowel diseases, celiac disease, and NSAID-induced ulcers.
1.2 Diagnostic Approaches for Leaky Gut
As of November 2024, leaky gut syndrome is not recognized as an independent disease. Consequently, there is no standardized diagnostic test for its diagnosis. However, several tests can indicate increased intestinal permeability, including the sugar test, zonulin, alpha-1-antitrypsin, I-FABP (intestinal fatty acid-binding protein), and biopsies. You can find more about the different diagnosis tools here.
2. Causes of Leaky Gut Syndrome
The causes of leaky gut are diverse and range from dietary factors to bacterial imbalances in the gut, certain medications, and stress. The following sections provide an in-depth look at potential causes:
2.1 Diet
A diet high in fats and sugars but low in fiber can contribute to the development of leaky gut. This so-called “Western-style diet” has been shown to weaken tight junctions in the digestive system (2). A disrupted intestinal barrier allows harmful substances, undigested food particles, bacterial components, and pathogens to enter the bloodstream, triggering an immune response. This can lead to a systemic inflammatory reaction, which may cause various symptoms and increase the risk of disease development.
Additionally, a low-fiber diet is associated with an altered gut microbiome. Fiber serves as a primary food source for beneficial gut bacteria. When these bacteria are deprived of their nutrients, they may die off, allowing less beneficial bacteria to take their place. A negative shift in the gut microbiome, known as dysbiosis, can further increase intestinal permeability and trigger immune reactions.
2.2 Infections
Infections, particularly those affecting the gastrointestinal tract, can significantly compromise the integrity of the intestinal barrier, contributing to the development of leaky gut. Pathogens such as viruses, bacteria, or parasites can attack the mucus layer and trigger inflammatory processes. These inflammations weaken the tight junctions—the structures responsible for maintaining an intact barrier.
Moreover, many pathogenic microorganisms produce toxins that directly damage intestinal cells and increase gut permeability. As a result, endotoxins, undigested food particles, and other harmful substances can enter the bloodstream, leading to systemic inflammatory responses and long-term health issues. Antibiotics used to treat infections can also disrupt the gut microbiome, potentially contributing to the development of leaky gut (3).
2.3 Exogenous Factors
The consumption of alcohol, nicotine, and certain medications can significantly impair intestinal barrier health and promote leaky gut.
Alcohol has a toxic effect on the mucous membrane of the gastrointestinal tract and weakens the tight junctions that connect the intestinal cells to each other. This increases the permeability of the intestinal wall, allowing harmful substances such as endotoxins to enter the bloodstream. (4)
In addition, alcohol disrupts the composition of the intestinal microbiota, which puts additional strain on the barrier function. (5)
Nicotine can also have a negative impact on gut health by contributing to the development of bacterial overgrowth, among other things (6). Nicotine also has an effect on blood pressure (7), which can lead to altered blood circulation in the intestinal mucosa. This can hinder the regeneration of intestinal cells and weaken the protective function of the intestinal wall.
Medications such as painkillers (also known as non-steroidal anti-inflammatory drugs (NSAIDs)) and antibiotics are also known to compromise intestinal integrity. Antibiotics and NSAIDs can severely disrupt the balance of gut flora and reduce protective bacterial strains. This creates an unfavorable environment in which pathogenic bacteria can thrive and further weaken the barrier. Long-term use of NSAIDs can also damage the mucus layer and cause micro-inflammation (8).
A conscious approach to alcohol, nicotine, and medications is essential for maintaining gut health and reducing the risk of leaky gut.
2.4 Lifestyle and Stress
Chronic stress and an unhealthy lifestyle can significantly contribute to the development of leaky gut.
Stress affects gut health through multiple mechanisms. It triggers the release of stress hormones such as cortisol, which reduces blood flow to the gastrointestinal tract and promotes inflammation. Additionally, stress alters the gut-brain axis and microbiota composition. An imbalanced microbiome fosters the growth of harmful bacteria that produce toxins, further impairing the intestinal barrier.
Other lifestyle factors, such as lack of sleep, physical inactivity, and an imbalanced diet, also play a role in leaky gut. Sleep deprivation reduces the body’s ability to regulate inflammation (9) and regenerate the intestinal mucosa. Lack of physical activity can slow intestinal motility, leading to inefficient elimination of harmful substances.
3. Therapy
3.1 Diet & Lifestyle
A fiber-rich diet including fruits, vegetables, whole grains, and fermented foods is essential for maintaining intestinal barrier integrity. These foods support gut health by promoting the production of short-chain fatty acids (SCFAs), which serve as an energy source for enterocytes and help maintain gut integrity. Avoiding pro-inflammatory foods is also crucial.
A healthy lifestyle that includes adequate sleep, regular exercise, and a balanced diet is fundamental for gut health. Stress management techniques such as meditation or yoga may also be beneficial.
3.2 Supplements
Certain supplements may help restore gut balance and improve barrier integrity. These include zinc, L-glutamine, butyrate (an important SCFA), myrrh, activated charcoal, and specific probiotics.
Zinc can strengthen tight junctions (10), L-glutamine supports the integrity of the intestinal mucosa (11), and butyrate serves as an energy source for intestinal cells. Myrrh helps stabilize the intestinal wall (12), while activated charcoal has anti-inflammatory properties (13).
Probiotics commonly used for leaky gut include Saccharomyces boulardii CNCM I-745 and Escherichia coli Nissle 1917. These strains help stabilize the gut microbiota (14).
4. Summary
The causes of leaky gut are as diverse as its treatment options. Managing leaky gut should always be done in consultation with a physician or healthcare professional to ensure the best possible outcomes. A thorough assessment of the underlying causes is essential for developing an individualized treatment plan.
References
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- Shapiro H, Goldenberg K, Ratiner K, Elinav E. Smoking-induced microbial dysbiosis in health and disease. Clin Sci (Lond). 2022 Sep 30;136(18):1371-1387. doi: 10.1042/CS20220175. PMID: 36156126; PMCID: PMC9527826.
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- Terciolo C, Dapoigny M, Andre F. Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption. Clin Exp Gastroenterol. 2019 Feb 11;12:67-82. doi: 10.2147/CEG.S181590. PMID: 30804678; PMCID: PMC6375115.
