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Heal Leaky Gut
July 23, 2021 Bogdan Popa, M.D.

How To Heal Leaky Gut

Article Highlights

  • Functional medicine seeks to uncover imbalances in the gut as a potential root cause of disease.
  • The gut is lined by a single layer of cells, called enterocytes which provide a barrier between the outside world and inside the body.
  • When the tight junctions between enterocytes become loose, or leaky, unwanted molecules make their way into the body leading to inflammation and disease.
  • Leaky gut is also known as leaky gut syndrome or, clinically, as intestinal permeability.
  • Leaky gut is not an on or off condition; the degree of leakiness is dynamic. Some amount of leakiness may actually be good for reasons such as nutrient absorption.
  • Zonulin is a measurable protein from the tight junction that can be measured in the blood.
  • Symptoms of leaky gut include digestive symptoms and systemic symptoms. Leaky gut may be a root cause to autoimmune and metabolic disease.
  • Leaky gut, or a gut that is too leaky, may be caused by a poor diet composed of highly processed foods, stress, alcohol, gluten, xenobiotics, medications and other factors.
  • Healing leaky gut requires a combination of diet and lifestyle change.
  • A diet to promote a healthy gut barrier includes eating whole foods, a wide variety of plant foods and meeting nutrient needs.
  • Reducing stress, incorporating appropriate exercise, sleep, and limiting exposure to toxins are some foundational lifestyle components for healing.
  • Supplements are an important and helpful tool for reversing leaky gut and overall gut health and healing.
  • Helpful supplements include: glutamine, butyrate, zinc carnosine, licorice, phosphatidylcholine and many others.

Functional medicine is root cause medicine. When searching for the underlying factors and contributors to symptoms or disease, we always consider the gut. The health of the gut informs the health of the entire body because it is needed for delivering nutrients into the blood, detoxification, immunity and so much more.

When gut health is out of balance, we might experience digestive issues, cognitive issues (brain fog), skin issues, mood issues (anxiety, depression), inflammation (joint pain) and a host of other symptoms. One reason behind this is intestinal permeability, commonly referred to as leaky gut.

We used to think about leaky gut as a condition that you either had or didn’t have, but now we see the system as much more complex and dynamic. Today’s article will dive into the details and answer the questions: 

  • What is leaky gut? Or what is leaky gut syndrome?
  • What are the symptoms of leaky gut?
  • What causes leaky gut?
  • What heals leaky gut and improves gut health?

This topic is incredibly important. Reversing leaky gut is foundational for your health exploration and healing journey. Let’s dive into all of the details and what you can do in your own life, right away.

What Is Leaky Gut, Leaky Gut Syndrome Or Intestinal Permeability?

The gut is an important interface between the external environment and our own body. It’s quite amazing then that this interface is made of the mucosal lining, which is the lining of the intestinal tract (specifically the small intestine) and it is made of only a single layer of cells.

These cells, called enterocytes, have the huge responsibility of absorbing important nutrients and molecules into the body, while keeping the trillions of bacteria, fungi and viruses residing in the gut out of the bloodstream.

If you think about it, the digestive tract is really outside of the body. In this way, it acts much like the skin to create a barrier protecting the immune system and all of our organs.  

Leaky gut is the state where the spaces between the enterocytes, called tight junctions, are no longer tight. The tight junction is the glue that holds the cells together and is made of proteins such as occludin, zonulin, claudin and JAM proteins. (Source 1)

Figure 1: In the picture above, you can see two adjacent intestinal cells (enterocytes). The space between the two cells is in white – called the paracellular space. Zonulin (Z01/2), Claudin, Occludin and the JAM family proteins regulate how permeable the paracellular space is – i.e., intestinal permeability or “leaky gut.”

In this state of increased intestinal permeability or hyperpermeability, organisms, toxins, proteins or pathogens which are normally not absorbed are able to pass through the enterocyte intestinal layer and barrier and enter the body. Once in our blood circulation, these unwanted molecules or organisms, trigger and immune reaction and inflammation in the body leading to symptoms and disease in different parts of the body. (Source 2)

How do I know if I have leaky gut? What are the best tests to measure leaky gut?

Test for Zonulin:

Zonulin is a hormone discovered in the year 2000 as a key regulator of intestinal permeability. (Source 3). Zonulin increases intestinal permeability by loosening the tight junction structures between the enterocytes (cells lining the gut). It’s now possible to measure zonulin in the stool or blood and this was used for several years as a diagnostic marker for leaky gut or as an intestinal permeability test.  

More recent thinking in functional medicine acknowledges that zonulin levels tend to fluctuate, suggesting that leaky gut is neither an on or and off condition. The system may be adaptive to current conditions in the digestive tract and be leaky at some times and less leaky at others. Antibodies to zonulin may be another marker to consider in assessing for dysfunction in the system. (Source 4)

Test for LPS “aka” endotoxin:

Lipopolysaccharides (LPS) are molecules making up the outer shell of gram-negative bacteria, a general class of bacteria that make up the majority of the gut flora. Measuring assays for LPS in food are a common way to test for contamination with the gram negative bacteria E. coli for example, to prevent food poisoning.

LPS is also known as “endotoxin” and it strongly stimulates our innate immune system to respond to an infection when it is present in our circulation. Fever and malaise ensue rapidly. Lipopolysaccharides, or endotoxins, are also a very direct way to measure the degree of intestinal permeability when they are in higher levels in the circulation than normal but not enough to trigger the full immune response above.

What could increase levels of LPS in the circulation? Some triggers include: gluten, high fat diets and alcohol (especially binging). These are all well known to cause leaky gut and spikes in LPS endotoxin levels in the blood.

LPS testing is difficult to obtain, but it is actively studied in an attempt to make it commercially available for human clinical measurements.

Takeaway: When thinking about leaky gut as a dial, instead of an on/off switch, we still need to consider that many factors of modern life turn the dial toward leaky gut. It may take some intentional strategies to balance the system. I’ll dive into all of these details below, but first let’s look at leaky gut symptoms and the associated disease states.

Leaky Gut Symptoms

Leaky gut symptoms may affect the whole body, not just the digestive system itself. Here are some common symptoms associated with leaky gut: 

Gastrointestinal symptoms:

Systemic symptoms of leaky gut may include:

In addition to these digestive and general symptoms, leaky gut is associated with a wide range of autoimmune, metabolic and other diseases or conditions. These include: 

There are likely more, but you get the point. Gut health and the function of the gut barrier affect the entire body.

A note on autoimmunity: Autoimmune disease occurs when the immune system mistakes the body’s own tissue as a foreign invader. This is called molecular mimicry and leaky gut is a root cause of its occurrence.

Leaky gut is how the foreign proteins enter the body in the first place and when those proteins resemble human proteins (molecular mimicry), the body gets confused. There need to be three factors in order for autoimmune disease to develop: a genetic predisposition, an environmental trigger and leaky gut.

Let’s peel back another layer to understand what causes intestinal permeability.

Leaky Gut Causes

In short, our modern world drives leaky gut. We eat a poor quality, inflammatory diet, have imbalances in the microbiome (dysbiosis), are exposed to toxins on a daily basis, take medications that disrupt the gut and are under an incredible amount of stress. All of this contributes to leaky gut.

Dr. Kara Fitzgerald, a well known authority in the world of Functional Medicine,  has organized a very comprehensive list of factors that increase (and decrease) intestinal permeability in this article.

Let’s discuss the main concepts here, however.

Diet plays a huge role in the development of leaky gut. What we eat influences the organisms that live in our digestive system, can carry pathogens into the system and even affect the immune system, most of which is housed in the gut itself. A standard American diet, or SAD diet, is high in inflammatory fats and sugar, while low in the nutrients needed to maintain a healthy gut lining, including vitamin A and zinc.

In addition, a SAD diet tends to be low in whole, colorful plant foods required for the proliferation of beneficial bacteria and other beneficial organisms. Not only is our diet generally low in the amount of flora and fiber we need but possibly as critical, our diet lacks diversity when it comes to plants.  We now know that diversity of plants in the diet is associated with lower mortality and disease. 

When we have leaky gut, food proteins that haven’t been fully digested enter the body, causing a sensitivity to that food. When we continue to eat foods we are sensitive to, inflammation increases.

A well-known example of this is gluten. We know that gliadin, a component of gluten found in wheat and other gluten-containing foods increases zonulin, and therefore leaky gut. (Source 3) Those who don’t have celiac disease, but have non-celiac gluten sensitivity, also have increased levels of zonulin. (Source 28)

In order to dial down leaky gut, here are some foods to decrease or eliminate in your diet:

  • Processed food and fast food
  • Sugar – soda, candy, baked goods
  • Alcohol
  • Processed Gluten – wheat, rye, spelt. For those individuals who are sensitive, they need to decrease allforms of gluten, even whole food forms such as rye kernels, farro and spelt berries.
  • Artificial sweeteners
  • Food additives and preservatives

In addition to these dietary strategies, here are other factors that increase intestinal permeability that you may want to consider reducing, eliminating or treating:

  • Eating late at night – (especially in conjunction with alcohol) causes and increase in leaky gut 
  • Infections or overgrowth, including:
    • Parasitic infections
    • Klebsiella (bacterial) infection
    • Small intestinal bacterial overgrowth (SIBO)
  • Xenobiotics and environmental toxins such as:
    • Bisphenol-A (BPA) found in plastics, food packaging and receipts. (Source 29)
    • Pesticides including glyphosate (Round-up) often sprayed on conventional corn, soy and wheat. (Source 30)
    • Mycotoxins from mold exposure in the environment or in food. (Source 31)

As you can see, there are a host of contributors to leaky gut, but many of them are modifiable and within your control to change. Please speak with your doctor before changing or discontinuing any medication.

Now, let’s talk about how to heal your gut.

Leaky Gut Treatment

Nutrition for leaky gut

In addition to decreasing the factors that drive intestinal permeability, there are many solutions that help to keep tight junctions tight and the dial on leaky gut turned down lower. 

Certain foods and diet change are incredibly important to heal leaky gut. Since we eat three times per day, and often more, you have many opportunities to make choices that support gut health and impermeability.

We know that highly processed, modern foods help to create leaky gut conditions and that we can turn this around by returning to more traditional ways of eating.

Begin by eating whole foods, including lots of colorful plant foods each day to provide prebiotic food to your microbiome. Here are some specific foods to consider adding to or increasing in your diet.

  • Berries – raspberries, blackberries, blueberries, cranberries etc.
  • Pomegranates
  • Green tea
  • Cruciferous vegetables – kale, collard greens, broccoli, cauliflower, cabbage, etc.
  • Garlic
  • Ginger
  • Olive oil
  • Organic dairy – butter, ghee, whey protein (if dairy is tolerated)
  • Herbs and spices

Plant foods are particularly important for microbiome health. I recommend trying to eat 40, or more, different plant foods each week in order to achieve the diversity factor discussed earlier. These can include a variety of vegetables, fruits, whole grains, legumes, nuts, seeds, herbs and spices. In addition, quality animal foods such as eggs, liver and sustainably raised meats (preferably grass-fed or pastured) will help to provide zinc, vitamin A, Vitamin D and other nutrients essential for maintaining a healthy intestinal lining and immune system.

Lifestyle for leaky gut

In addition to these diet strategies, lifestyle also plays a key role. I cannot emphasize these lifestyle components enough! They include:

  • Minimizing exposure to environmental toxins
  • Managing stress using meditation, prayer, creative outlets and bodywork
  • Getting enough, quality sleep. Disrupted circadian rhythms, in night shift workers for example, increase intestinal permeability.
  • Spending time outdoors in the sunshine
  • Exercise and movement

These daily health habits are helpful on so many levels, including, or perhaps most importantly, from the way that they impact gut health and keep our gut lining more impermeable.

Building a solid foundation of a nutritious diet and healthy lifestyle will be supportive of healing the gut and preventing disease. However, many of us may need additional support to heal and repair the digestive system. Supplements help to improve your gut health, and overall health, in less time than diet and lifestyle changes alone. In fact, supplements are a great bridge while you get the other pieces in place.

Leaky Gut Supplements

As you may know, I am passionate about bringing high quality, effective and absorbable nutrients to you to support your health. When it comes to gut health, and specifically healing leaky gut, there are many nutrients and botanicals to choose from. Let me walk you through the science behind some of my favorites.

L Glutamine benefits for leaky gut:

A glutamine supplement, or l glutamine, is my top choice for healing leaky gut. Epithelial cells regenerate every 2-3 days and, surprisingly, they prefer l-glutamine as their primary source of fuel. Glutamine is an amino acid found in protein foods with the highest levels coming from foods including meat, eggs and dairy. Higher doses can be achieved through supplementation and are quite effective. 

Glutamine plays an important role in the repair stage of leaky gut healing. L-glutamine is shown to preserve the mucosal gut barrier by protecting the tight junctions. (Source 37)

In a randomized controlled trial, participants with Crohn’s disease were given glutamine supplements or whey protein, a dietary source of glutamine. Both groups showed improvements in their intestinal permeability. (Source 38)

In another study, glutamine supplementation was given to patients with irritable bowel syndrome (IBS), which is associated with leaky gut. The protein, claudin-1 was measured as a marker of intestinal permeability and improved with the glutamine supplementation. (Source 39)

For supplemental l-glutamine, the therapeutic dose begins at 5 grams per day preferably on an empty stomach or between meals. Glutamine is often combined with the other supplements discussed below.

Butyrate benefits:

Butyrate, or butyric acid, is a short chain fatty acid produced by beneficial, probiotic bacteria in the colon from the fermentation of dietary fiber. Butyrate, along with glutamine, provides an energy source to the enterocytes that line the digestive tract. Increasing butyrate through food (high fiber intake) or supplements, helps to strengthen and heal the mucosal lining of the digestive tract.

Butyrate foods include: butter and ghee. Eating a diversity of high fiber, prebiotic foods will help to increase butyrate production in the colon. (Source 40) In addition, a butyrate supplement may be used to speed up the healing process. 

Supplemental dosages range from 400 to 1000mg with food.

Zinc Carnosine benefits:

Zinc is an important nutrient for the immune system and GI health. Zinc carnosine is a supplemental form of zinc that has been shown to prevent gut permeability caused by NSAID medication and other factors. (Source 41)

In a small randomized controlled trial, participants received zinc carnosine, colostrum, zinc carnosine plus colostrum or placebo prior to exercise. Colostrum, is the nutrient and immunoglobulin-rich first milk that may be used supplementally to promote improved gut immunity. Gut permeability naturally rises after exercise and in this study, both zinc carnosine and colostrum inhibited the rise in permeability by 70 percent. (Source 41)

A typical supplemental dose is around 75 mg of zinc carnosine, providing 16 mg of zinc itself. Always take zinc with food to avoid digestive issues.

Licorice benefits:

Licorice is an herb that is considered mucilaginous as it helps to increase mucus production, soothing the GI tract. Licorice has been used traditionally in Chinese Medicine for digestive symptoms, as an anti-viral and antimicrobial and to support hormonal balance. Licorice in its whole form may increase blood pressure, but deglycyrrhizinated licorice, or DGL, is a form that doesn’t have this effect.

DGL has further effects on the gastrointestinal system, including antispasmodic action and intestinal relaxation. (Source 42)

For these reasons, DGL is often a top choice for functional medicine practitioner to support the healing of leaky gut. Chinese Medicine dosages of licorice range from 8-15 grams in a decoction and up to 100 grams for specific diseases. DGL is typically dosed in the range of 150-300 mg daily, and even higher dosages used for short term healing are safe (up to 1800mg per day has been studied as safe to use for 4 weeks).

Phosphatidylcholine benefits:

Phosphatidylcholine is an important phospholipid found in every cell of the body. The phosphatidylcholine structure, composed of a head containing phosphorus and two fatty tails, provides it with the ability to create a barrier. Phosphatidylcholine is used in many supplements here at Core Med Science because it forms the liposomal structures (spheres) responsible for the increase in absorption of various nutrients from the digestive system into the body, and ultimately into the cells that need the nutrition.

In the digestive system itself, phosphatidylcholine is important for the structure and function of the enterocytes themselves. In fact, it’s estimated that phosphatidylcholine comprises around 90 percent of the mucus membrane lining in the gut. This mucus membrane stands between the harmful bacteria (and other organisms) in the gut and the enterocytes creating a protective barrier.  A phosphatidylcholine supplement may help to improve the intestinal barrier (decrease leaky gut) against pathogens such as Clostridium difficile.(Source 43)

Additional research has been done in people with ulcerative colitis, an autoimmune disease that affects the mucosal membrane of the colon. Phosphatidylcholine supplementation was shown to improve symptoms, induce intestinal healing and even put patients into remission. (Source 44, 45)

I discuss the benefits of phosphatidylcholine as a supplement in my article Phosphatidylcholine Benefits: Brain, Liver, Gut And Cellular Function. 

Elemental diet benefits:

An elemental diet is one composed of just amino acids, fats, vitamins and minerals. It is a way to give the bowel a rest and make digestion very easy. Elemental diets have been found to be very useful in patients with small intestinal bacterial overgrowth (SIBO) and Crohn’s disease.

Additional supplemental nutrients, phytonutrients and herbs may be beneficial for improving intestinal permeability, heal leaky gut, and bringing balance to the tight junctions. These include:

  • Vitamin A
  • Vitamin D
  • Vitamin C
  • Vitamin E
  • Folate
  • Selenium
  • Amino acids including glycine, arginine and glutamine
  • N-acetyl-D-glucosamine
  • Alpha lipoic acid
  • N-acetyl cystine (NAC)
  • EPA and DHA from fish oil
  • Betaine
  • Quercetin
  • Astaxanthin
  • Berberine
  • Frankincense
  • EGCG from green tea
  • Curcumin
  • Marshmallow
  • Oregano
  • Slippery elm
  • Thyme

While some amount of leakiness in the gut is normal because it helps us to absorb certain nutrients, adapt to the foods we are eating and likely for other reasons that we don’t fully understand yet, the vast majority of us have guts that are too leaky.

Our modern, stressful lives, fast food diets, exposures to medications and toxins in the environment contribute to a decline in integrity in the gut barrier meant to protect the body from harm. When this barrier is compromised, organisms and proteins that are meant to stay in the gut, digest fully or pass through the colon enter the body and signal the immune system. The result is inflammation, autoimmunity and chronic disease.

It was Hippocrates who, over 2000 years ago, said that “all disease begins in the gut.” And was most certainly right. Now, we have the science to prove it.  

The good news is that many of the factors that create a leaky gut situation are reversible and entirely in our personal control. In addition, we have an array of supplement options with a history of use for restoring gut integrity and function.

This is truly functional medicine at its best. Leaky gut is often a root cause of disease and when reversed, repaired and healed, the rest of the body heals too.

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