Medicinal Herbs and ADHD


Leaky Gut Syndrome: Symptoms, Causes, and Testing

Key Topics: Digestive Health
February 19, 2022 • 5 min read

What is “Leaky Gut”?

Leaky gut syndrome, also known as intestinal hyperpermeability, occurs when the lining of the small intestine is impaired, allowing larger molecules to bypass the gut barrier and into the bloodstream. These molecules may be components of ingested food particles, bacteria, and foreign substances.1

The gut barrier is composed of epithelial and immune cells that interact with the microbiota to form a protective barrier from the external environment.2,3 Goblet cells produce a thick layer of mucus that covers the epithelial cells, forming a barrier that provides additional protection from numerous environmental challenges, including: bacteria and toxins from reaching the epithelial surface.2,4 This layer is held together by tight junctions and acts as part of the immune system’s first line of defense in the gut.2,5 In a healthy functioning gut, these tight junctions help the intestinal barrier regulate nutrient, electrolyte, and water absorption while blocking the intake of harmful substances.6,7 This barrier is like the gut’s personal security guard; it selectively welcomes certain substances and nutrients for absorption and acts as a protector against harmful substances that enter from the lumen.6,7

When a leaky gut lacks this security perimeter, the immune system initiates what becomes chronic, systemic inflammation. Chronic inflammation disrupts the mucous layer of the intestinal lining, and the tight junctions become compromised. This increases permeability, and, in turn, allows these larger molecules to pass between epithelial cells and into the bloodstream.6,7

When certain particles leak through the GI into the bloodstream, they may trigger excessive immune responses, and have associations with many symptoms as outlined below.

Why is a Healthy Gut Barrier Important?

The health of the gastrointestinal tract is deeply connected to what happens in various other body systems. When leaky gut occurs, inflammation can cause the release of cytokines and neurotransmitters. These molecules are able to travel systemically through the bloodstream, wreaking havoc on the immune system and even crossing the blood brain barrier, influencing brain function.8 Without proper elimination, these toxins may build up in the body, which may lead to serious health conditions over time.

Symptoms Associated with Leaky Gut:

  • Bloating
  • Flatulence
  • Diarrhea
  • Constipation
  • Brain fog
  • Headaches or Migraines
  • Difficulty concentrating
  • Skin irritations (acnes, rosacea, eczema)
  • Anxiety
  • Depression
  • Hormone imbalance
  • Joint pain (rheumatoid arthritis, fibromyalgia)
  • Food sensitivities
  • Fatigue

What Causes Leaky Gut?

There is limited data surrounding the causes of leaky gut, and that exact cause is still unknown. However, studies show the following factors are associated with susceptibility to leaky gut.

Age and Genetics

Some individuals may be predisposed to developing intestinal permeability due to their genetic makeup. They may be more sensitive to environmental factors that could trigger autoimmune responses.9,10 The CARD15 3020insC mutation may be a genetic factor involved with intestinal permeability in families specifically with IBD or Crohn’s disease.11

Additionally, during the aging process, the gut barrier naturally tends to lose its resilience, increasing susceptibility.12


A diet high in inflammatory foods, refined carbohydrates, saturated fats, high sugar, excessive alcohol, and food allergens or triggers of food intolerances may be a cause of leaky gut.1 Consuming foods to which one may be allergic or sensitive may encourage the immune system to overproduce antibodies that attack its own tissues. This could lead to chronic inflammation and disease other health problems.13,14

Consuming high amounts of gluten, especially if allergic or intolerant, can also be problematic. Gliadin is a class of protein found in gluten that can stimulate a stress response, what is often called the innate immune response. This response releases zonulin, which can increase intestinal permeability.15,16 Zonulin is just one of many tight junction proteins that help regulate the permeability of tight junctions in the digestive tract. The over-release of zonulin activates an intracellular pathway in the intestinal cells. This increases the permeability of the tight junctions, resulting in a leaky gut.16

Poor diet may also lead to nutritional deficiencies in magnesium, vitamin A, zinc, and vitamin D – all of which have been associated with impaired barrier integrity.13,17,18 Both short- and long-term magnesium deficiency can change the composition of the gut microbiota. This decreases the populations of beneficial bacteria such as Bifidobacteria, which may lead to negative alterations in the intestinal mucosal barrier.19,20


A sedentary lifestyle, high stress, and poor sleep patterns can affect epithelial barriers.21,22 This may be due to the gut-brain axis connection. The gut-brain axis communicates between the central nervous system and the gut microbiota.8,22,23

Toxin Burden

Buildup of toxins and toxicants from food, alcohol, environment, and medications can cause chronic inflammation. According to the National Toxicology Program, there are over 80,000 chemicals registered for use in the United States. People are exposed from air, water, household products, personal care products, pesticides, and herbicides. The excessive use of medications like NSAIDs (non-steroidal anti-inflammatory drugs) and antibiotics contributes to leaky gut and dysbiosis risk, furthering the potential toxin burden.24-26

Microbiome Dysbiosis

The gut microbiome is crucial in supporting the epithelial barrier and protecting against inflammatory diseases. When the microbiome is challenged, its physiology can change. This often leads to a dysbiosis state, increased risk of intestinal permeability, and developing autoimmune disease.8

Dysbiosis of the microbiome typically consists of a poor ratio of pathogenic bacteria to beneficial bacteria. Some of the pathogenic bacteria that have been shown to be contributors of leaky gut are Clostridium difficile and H. Pylori.2,27,28

Lastly, an overgrowth in yeast can also cause dysbiosis. Yeast is naturally found in the gut, but excess yeast growth can be a risk factor in developing leaky gut – potentially candida or a condition called small intestinal bacteria overgrowth (SIBO).26,29,30

Conditions Associated with Leaky Gut31,32

  • IBS, Crohn’s disease and ulcerative colitis (IBD)
  • Food sensitivities and intolerances
  • Autoimmune disorders
  • Diabetes
  • Asthma
  • Skin conditions (e., eczema)
  • Neurological conditions (e., depression, anxiety, Alzheimer’s disease, Multiple Sclerosis, Parkinson’s disease, autism)

Testing for Leaky Gut

Microbiome dysbiosis is strongly connected to intestinal hyperpermeability.7 Microbiome stool tests can help determine microbiome dysbiosis and provide a snapshot of the specific bacterial and fungal strains that inhabit an individual’s gut microbiome.

A solution is given with both mannitol and lactulose. In someone with a healthy gut lining, the mannitol should be easily absorbed.31 The test results would show mannitol in high levels. The lactulose should only be shown in low levels, as it is a larger molecule and only should be slightly absorbed.31 If the urine test results show low levels of mannitol and high levels of lactulose, this can indicate intestinal permeability or leaky gut.

Tests for zonulin levels in the blood. Intestinal hyperpermeability can be indicated if zonulin levels are high in the serum. Although, this testing method may not be always reliable as zonulin levels can naturally fluctuate.34

Tests the IgG and IgA antibodies against the tight junction proteins that leak into the blood (zonulin, occludin, actomyosin). This is shown to be more accurate than the serum zonulin.34

May be useful in discovering food sensitives that are contributing to symptoms. The Elimination Diet is also a great tool to help identify what foods are causing what symptoms.

Addressing Leaky Gut Syndrome

Restoring gut health involves establishing a healthy diet and lifestyle which can significantly repair the microbiome and the intestinal lining.31

Incorporating lifestyle therapies like stress management, breathing exercises, meditation, yoga, exercise, and vagus nerve stimulation may improve symptoms and quality of life for individuals with leaky gut.35 The vagus nerve is a key component in the parasympathetic nervous system, which includes a variety of body functions like mood, immune response, heart rate, and digestion.35-37 The vagus nerve extends from the brain stem all the way to the colon, communicating signals and information from the liver, heart, lungs, and gut to the brain.35-37 It can help reduce the fight-or-flight response by stimulating the rest-and-digest parasympathetic nervous system.35 This can reduce digestive inflammation as well as reduce intestinal permeability.36 There may be ways to stimulate the vagus nerve including deep breathing, meditation, yoga, movement, cold showers, and even humming or singing. Although, more clinical studies need to be done to assess vagus nerve stimulation as an intervention for leaky gut.35,38,39,40,41

Replacing a poor diet with anti-inflammatory whole foods may help in restoring nutritional deficiencies as well as supply the gut with beneficial phytonutrients and antioxidants for healing. To help facilitate digestion, incorporating digestive enzymes, hydrochloric acids, and bile salts in the diet may be useful.

Repopulating the microbiome with probiotics and prebiotics can also support the growth of beneficial bacteria. Probiotics can be in the form of a supplement or found in fermented foods like yogurt, kombucha, kefir, sauerkraut, or kimchi. Prebiotics are important for feeding the beneficial bacteria and helping them thrive in the microbial environment. Examples of prebiotics include inulin, Jerusalem artichoke, garlic, onion, and oats.

Additional Nutrition and Herbal Support

For further nutrition and herbal support for leaky gut, there are a few different options to speak with your healthcare provider about. Herbs like slippery elm, licorice, and chamomile contain constituents that may be beneficial in reducing intestinal permeability. Specifically, this is due to tannin components which have anti-inflammatory activity in the upper GI tract.7

Slippery elm also soothes the digestive tract and can boost production of short chain fatty acids (SCFAs).7 Butyrate is an important SCFA that serves as an energy source for cells in the colon and has shown to protect and repair the intestinal barrier.42

Berberine also has many GI benefits including being an antidiarrheal and anti-inflammatory agent that helps in protecting intestinal mucosal barrier function.26 It has an antimicrobial effect that can inhibit harmful bacteria in the microbiome while not disrupting the good bacteria.7,43

L-Glutamine is one of the most abundant amino acids in the body. It is involved in many metabolic processes, but it is particularly critical in the development and regeneration of intestinal cells.28,39 It provides energy to help rebuild the mucosal lining.44,45

Clinoptilolite is an absorbent material that helps bind naturally occurring toxins in the body and prepare them for elimination. This material has been shown in cell studies, animal models and clinical trials for its ability to support the gut barrier integrity under stressed conditions, protect the mucosal barrier and help repair damage.46-49


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