Subscribe to the Magazine for free.
Subscribe for free to keep reading! If you are already subscribed, enter your email address to log back in.
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Are you a healthcare practitioner?
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.

A Functional Medicine Protocol for Leaky Gut Syndrome

Medically reviewed by 
A Functional Medicine Protocol for Leaky Gut Syndrome

In 2018, over 70,000 Americans participated in the National GI Survey, which concluded that two-thirds of individuals experienced at least one weekly gastrointestinal (GI) symptom, and nearly 60% had at least two concurrent symptoms. The prevalence of GI symptoms and disorders is astounding and should not go unnoticed.

Understanding the mechanisms involved in disease development, we know that diseases can both cause and be caused by a disruption in the intestinal mucosal barrier. This disruption, referred to as intestinal permeability or leaky gut, is the widening of the spaces between the cells lining the small intestine and can be influenced by various factors. If you have gut health problems, you likely have leaky gut syndrome. This article will discuss what leaky gut is and how you can address it.


What is Leaky Gut?

While leaky gut has not yet been recognized as a distinct medical diagnosis, this does not mean that it is not real. There is plenty of research that acknowledges intestinal permeability and its underlying mechanisms. In fact, the concept of leaky gut has received increasingly more attention in the medical world because of its associations with numerous health conditions, including non-GI conditions like asthma, Alzheimer's, and diabetes.

The intestinal barrier comprises a single layer of epithelial cells linked together by tight junction proteins. This barrier is selectively permeable, meaning that it allows only the absorption of digested nutrients and water in a healthy state. When the tight junctions are disturbed, the spaces between the cells enlarge, and larger molecules can enter the bloodstream. The immune system recognizes these larger proteins as foreign, triggering exaggerated immune responses and systemic inflammation.

Leaky Gut Syndrome Symptoms

Many of the symptoms of leaky gut manifest in the gut due to increased intestinal inflammation. These symptoms may look very similar to irritable bowel syndrome (IBS) and include the following:

  • Abdominal pain
  • Bloating
  • Change in bowel movements patterns: constipation, diarrhea, or both
  • Food intolerances/sensitivities
  • Gas
  • Indigestion

Increased intestinal permeability can also contribute to these symptoms outside of the digestive tract:

  • Brain fog and difficult concentration
  • Fatigue
  • Headache
  • Joint pain
  • Mood disorders: depression, anxiety, ADD/ADHD
  • Nutritional deficiencies
  • Skin problems: acne, rashes, eczema, psoriasis

There are also studies suggesting that leaky gut may be associated with the following conditions (1, 2):

What Causes Leaky Gut Syndrome?

Zonulin is a protein secreted by the intestinal tract and is currently the only known protein that reversibly regulates intestinal permeability by controlling the tight junctions between epithelial cells. Environmental triggers and lifestyle factors (outlined below) can stimulate the upregulation of zonulin and increase intestinal permeability. (3)


Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen and aspirin, chemotherapy agents and radiation therapy, and frequent antibiotic use can cause leaky gut by inducing intestinal inflammation and decreasing diversity within the gut microbiome. (4-8)


Western diets, characterized by excessive inflammatory foods (i.e., simple carbohydrates, saturated/trans fats, alcohol) and insufficient fiber, increase intestinal inflammation and dysbiosis.

Multiple studies have found a correlation between food sensitivities/allergies and intestinal permeability (9, 10). Of the most common food allergens, gliadin, a protein component of wheat that can directly upregulate the zonulin protein, is most strongly connected to leaky gut (3).

Intestinal Dysbiosis

Bacterial exposure through intestinal infections and overgrowth increases zonulin production and stimulates intestinal permeability (3). Imbalances in the healthy balance of the gut microbiota lead to intestinal permeability and inflammation, unfavorable changes to intestinal motility, and more severe GI symptoms (11, 12).


Emotional and physical stress influence hormonal secretion patterns and nervous system function. These physiologic responses to stress can change the composition of the gut microbiome and inhibit intestinal healing mechanisms, leading to leaky gut. (13-15)

Environmental Toxins

Exposure to environmental toxins, including bisphenols, phthalates, heavy metals, and pesticides, contributes to increased oxidative stress, inflammatory responses, disruptions in healthy hormonal signaling, and imbalances in the gut microbiome. Together, these interruptions contribute to the progression of leaky gut.

Functional Medicine Labs to Test for Root Cause of Leaky Gut Syndrome

Researchers commonly use the lactulose-mannitol urine test to assess intestinal permeability. Currently, this test is not standardized for clinical practice and, therefore, not widely used by providers.

Most commonly utilized by functional practitioners to quantify intestinal permeability are zonulin measurements, which can be measured through stool or blood samples. Zonulin can easily be added to a comprehensive stool analysis, a test that can assess digestive function, quantify intestinal inflammation, and screen for intestinal infections and dysbiosis. Vibrant Wellness offers a Leaky Gut blood panel that directly measures zonulin levels along with antibodies to zonulin, actin, and lipopolysaccharide, which are all associated with leaky gut.

Blood panels can be ordered to screen for both food allergies and sensitivities. Food allergy panels measure IgE protein levels in response to common food allergens, whereas food sensitivity panels measure IgG/A protein levels. Panels can often be customized to measure all three immune proteins for the most comprehensive assessment of adverse food reactions. Cyrex Lab's Array 3 is one of the most well-respected and accurate specialty labs that can identify gluten reactivity by measuring the immune response against the various protein components of wheat.

A salivary stress profile measures cortisol levels and diagnoses imbalances in the stress response.

The GPL-TOX profile screens for exposure to 173 toxic pollutants through a urine sample. It is often ordered in combination with this urinary glyphosate test.

Functional Medicine Protocol for Leaky Gut Syndrome


Dietary modifications will be one of the best ways to reduce inflammation and promote intestinal healing.

An anti-inflammatory diet can decrease intestinal inflammation and promote the closure of the intestinal tight junctions. The Mediterranean, DASH, and Paleo diets are all classified as anti-inflammatory diets. Core principles shared between these diets include limiting refined sugars and processed foods and incorporating fresh, whole fruits and vegetables and lean meats.

Any of these diets can be customized to your needs. Eliminating identified food allergies and sensitivities can eliminate specific dietary triggers of intestinal inflammation and support the healing process. Instead of being confined by dietary guidelines, finding a diet that works best for your body will lead to the most success in your healing journey.

Complementary and Alternative Medicine

There are a wide array of gut healing supplements utilized by functional doctors to promote intestinal healing. A few first-choice supplements typically recommended as part of a gut-healing protocol include:

  • Probiotics contain beneficial bacterial strains that promote a healthy intestinal microbiome balance. A balanced microbiome is known to aid in digestion, immune function, hormone/vitamin synthesis, and maintain intestinal barrier integrity.
  • L-Glutamine is an amino acid and primary fuel source for the cells that line the small intestine. L-Glutamine's role in cell turnover and intestinal healing is widely supported by research.
  • Vitamin D supplementation to optimize nutritional status is associated with improved immune function and decreased markers of intestinal permeability.

Moderate-intensity aerobic exercise improves the diversity of the gut microbiome and decreases intestinal inflammation. As exercise intensity increases, so do systemic cortisol levels, intestinal inflammation, and dysbiosis - so be mindful to avoid overexercising.

Circadian disruption correlates with increased intestinal inflammation, dysbiosis, and permeability. Prioritizing a healthy sleep routine for good quality sleep can support intestinal healing and reverse leaky gut. Tips for deep sleep include:

  • Go to bed and wake up at the same times each day of the week
  • Expose yourself to early morning light upon waking
  • Avoid blue light and strenuous activities 1-2 hours before bedtime
  • Sleep in a clean, quiet, cool, and dark room



Leaky gut syndrome, or increased intestinal permeability, is a condition characterized by compromised intestinal barrier function that allows the absorption of large proteins into systemic circulation. Leaky gut has been associated with many inflammatory systemic health conditions. If you suspect a leaky gut is contributing to your symptoms of dis-ease, consult an integrative healthcare provider who can work with you to identify and eliminate causative triggers with specialty testing, lifestyle modifications, and natural supplements.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
Learn More

Lab Tests in This Article

No items found.


1. Anderson, S. (2022, June 6). How to Talk to Your Patients About Leaky Gut: An Overview. Rupa Health.

2. Campos, M., MD. (2021, November 16). Leaky gut: What is it, and what does it mean for you? Harvard Health.

3. Fasano, A. (2012). Intestinal Permeability and Its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clinical Gastroenterology and Hepatology, 10(10), 1096–1100.

4. Bjarnason, I., Hayllar, J., Macpherson, A., et al. (1993). Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology, 104(6), 1832–1847.

5. Graham, D.Y., Opekun, A.R., Willingham, F.F., et al. (2005). Visible small-intestinal mucosal injury in chronic NSAID users. Clinical Gastroenterology and Hepatology, 3(1), 55–59.

6. Utzeri, E., & Usai, P. (2017). Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease. World Journal of Gastroenterology, 23(22), 3954.

7. Ciernikova, S., Mego, M., & Chovanec, M. (2021). Exploring the Potential Role of the Gut Microbiome in Chemotherapy-Induced Neurocognitive Disorders and Cardiovascular Toxicity. Cancers, 13(4), 782.

8. Ramírez, J.A., Guarner, F., Fernandez, L.A., et al. (2020). Antibiotics as Major Disruptors of Gut Microbiota. Frontiers in Cellular and Infection Microbiology, 10.

9. Ventura, M.R., Polimeno, L., Amoruso, A., et al. (2006). Intestinal permeability in patients with adverse reactions to food. Digestive and Liver Disease, 38(10), 732–736.

10. Bjarnason, I., Macpherson, A.J., & Hollander, D. (1995). Intestinal permeability: An overview. Gastroenterology, 108(5), 1566–1581.

11. Ciccia, F., Guggino, G., Rizzo, A., et al. (2017). Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Annals of the Rheumatic Diseases, 76(6), 1123–1132.

12. Canakis, A., Haroon, M., & Weber, H.A. (2020). Irritable bowel syndrome and gut microbiota. Current Opinion in Endocrinology, Diabetes and Obesity, 27(1), 28–35.

13. LoBisco, S. (2022, September 16). Gut-Brain Axis: Understanding The Gut-Brain Connection. Rupa Health.

14. Vanuytsel, T., Van Wanrooy, S., Vanheel, H., et al. (2014). Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut, 63(8), 1293–1299.

15. Costa, R.J.S., Kitic, C.M., & Gibson, P.R. (2017). Systematic review: exercise-induced gastrointestinal syndrome-implications for health and intestinal disease. Alimentary Pharmacology & Therapeutics, 46(3), 246–265.

Subscribe to the Magazine for free. to keep reading!
Subscribe for free to keep reading, If you are already subscribed, enter your email address to log back in.
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Are you a healthcare practitioner?
Thanks for subscribing!
Oops! Something went wrong while submitting the form.