Image by Silvia from Pixabay


Before you dive headlong into a leaky gut treatment, determine if leaky gut is really the issue. Officially known as “intestinal permeability,” leaky gut is a breakdown of the gastrointestinal barrier. When that gut lining is damaged, it can spark inflammation and immune attack. Leaky gut is a central hypothesis in integrative and functional medicine and a root cause of chronic illnesses. We will review the most popular blood and urine leaky gut tests available to practitioners and patients. Treat leaky gut with diet, supplements, and lifestyle to soothe the gut barrier and promote healing. Once leaky gut syndrome is fixed, chronic inflammatory diseases cool off and immune health will be restored.


We are grateful to our sponsor, Precision Point Diagnostics, for making this blog possible.


Struggling with joints that are achy and inflamed? Read my blog on leaky gut and joint pain.

What is Leaky Gut?

Intestinal permeability, or leaky gut syndrome, is now a more commonplace term. You, your friends, or colleagues may have heard about it. In leaky gut, the lining of the gastrointestinal tract becomes damaged. It develops little holes in it that allow harmful substances into the bloodstream where they don’t belong. When foreign substances arrive in the blood, it can set off an immune reaction, inflammation, and disease. Leaky gut is a breakdown in a person’s immune defenses that essentially opens that person up to the outside environment.

Intestinal permeability has been identified as having a role in diabetes, celiac disease, chronic fatigue, cancer, depression, obesity, irritable bowel syndrome, multiple sclerosis, and many more.1 It is a key factor in the development of autoimmune diseases.2 In integrative and functional medicine, leaky gut is an underlying cause that is often analyzed and treated to help turn around complex illnesses. Usually, practitioners treat and balance the gut microbiome, and digestion, and repair leaky gut to stop the progression, or even reverse, these illnesses.

Everyday Factors that Increase Leaky Gut3

  • Alcohol
  • Antibiotics
  • Aspirin
  • Dysbiosis (imbalanced gut microorganisms)
  • Non-steroidal anti-inflammatory medications
  • Stress
  • Unhealthy diet (high in sugar and refined carbohydrates, low in fiber)


Leaky Gut and Systemic Inflammation

You’ve probably heard that all disease begins in the gut. One of the reasons for this is leaky gut. When a person has leaky gut, their immune system is on red alert. Inflammation is surging through their system.4  This chronic inflammation can affect other parts of the body, such as the pancreas (type 1 diabetes) or the brain (Alzheimer’s, Parkinson’s, or multiple sclerosis).5

Leaky gut can let bad bugs roam free. When the gut barrier is weak and flimsy, harmful organisms and substances can breach the barrier, triggering extraintestinal infection. That means that an infection or imbalance in the gut can spread to distant sites outside of the gut, such as the brain, joints, or lungs. There are many, many bacteria in the gut. Most are beneficial, but some are harmful. Regardless, they are supposed to stay put. When they escape the gut, they can jump on the blood superhighway and land in far-off places where they don’t belong. This can set up infections in organs that are not equipped to deal with these gastrointestinal bugs, further adding to the inflammatory burden.

Photo by National Cancer Institute on Unsplash

Leaky Gut Tests

There are a few different ways that integrative and functional practitioners measure leaky gut. Routine leaky gut tests can be done with a blood or urine specimen. Practitioners often run these tests, but some can be purchased directly by the consumer. We will go over the pros and cons as well as some of the evidence behind them.

Lactulose: Mannitol Test for Leaky Gut

For this test, you drink a mixture of two sugars (lactulose and mannitol) and then measure these substances in the urine. Our bodies don’t metabolize these sugars, so it’s easier to measure what they do in the gut. If the gut barrier is strong, the “leaked” sugar molecules should be low in urine. If the gut barrier is leaky, the sugar molecules should “leak” from the gut and go high in urine. This is the leaky gut test commonly used in research studies.6 However, the drink is a deal-breaker for some patients. If you have a lot of bloating or are sensitive to many foods, this may not be the best test. Collecting urine for multiple hours can be a drawback. The benefit of this test is that you can take it in the comfort of your own home. Simply drink the solution and collect your urine.

Zonulin and Antibody Tests

Plasma zonulin is a well-researched marker of leaky gut, known for its role in the tight junctions (or connections) between cells of the gut lining. High zonulin opens up these junctions, resulting in leaky gut. Much of the research on celiac disease and leaky gut features the zonulin marker. Fecal zonulin can be found in some stool tests as an indicator of leaky gut.

The Advanced Intestinal Barrier Assessment test from Precision Point Diagnostics tells clinicians about leaky gut, the health of the gut lining, histamine excess, and gut dysbiosis. It measures plasma zonulin, plasma histamine, and diamine oxidase. When the gut barrier is unhealthy, histamine and DAO can be out of balance, which can also point to leaky gut.7-9

In addition, this panel measures IgA, IgM, and IgG antibodies to lipopolysaccharides (LPS), an inflammatory component of gram-negative bacterial cell walls. LPS antibodies are another sign of leaky gut because they show that bacteria from the gut are passing into systemic circulation and stimulating an immune reaction.1 This blood test can be ordered by healthcare providers. If you are a patient, you’ll need to ask your doctor to sign up for an account to order this test.

Other laboratories measure antibodies to zonulin, occludin, and actomysin as an indicator of leaky gut.


Food Sensitivity Testing

Another leaky gut test might surprise you. It’s a food sensitivities test. How can food sensitivities tell you about leaky gut? It is because people with leaky gut often show many, many food sensitivities. This test can do double-duty to detect food reactions as well as intestinal permeability. Look for IgG food antibody tests. These almost always require a blood draw, but some require a fingerstick only.

However, some clinicians find the results to be difficult to interpret. If the patient has leaky gut, it can be difficult to get a good read on the food reactions. This test is a good fit if food sensitivities are already suspected; for example if you (or a patient) struggle with congestion, ear infections, throat infections, skin reactions, constipation, diarrhea, or other gut symptoms. Integrative and functional medicine practitioners order these tests on their patients. They are also available from third party labs that sell directly to consumers. You can ask your doctor to order these tests for you or you can order them yourself and share your results with your doctor.


Clinicians, do you want to educate your patients about leaky gut and why it is so important to their health? Use this patient prep video package in your clinic or for outgoing emails to patients.


Invasive Leaky Gut Tests

It is possible to take biopsies from the human gut and measure their permeability in a laboratory setting. It is also possible to have endoscopic measurements using a fluorescent molecule or sensors to monitor for leaky gut.6 I can’t imagine undergoing this test when a simple blood or urine test could be done instead.



Leaky Gum Syndrome

The gut barrier is not the only barrier patients and practitioners need to be paying attention to. The lungs have a barrier. There is a blood-brain barrier. The mouth lining is a barrier. Skin is a barrier. Just like the wall standing high around a castle, these barriers protect your insides from the outside world. They are fundamental defensive barriers that help you resist infection. They also are enriched with immune cells that are ready for combat, just in case the barrier is breached by a foreign substance or organism.

Leaky gum syndrome,10 or leaky mouth, is a proposed condition of damaged gums and mouth tissues, which allows harmful microbes and inflammatory chemicals from the mouth into the bloodstream. Just like leaky gut, if the mouth barrier is broken down and damaged, harmful substances can get through the mouth lining and into the bloodstream where they can cause harm. Up to 50% of adults have periodontal disease, meaning leaky gums could affect a huge percentage of people. Similar to intestinal permeability, gum permeability can affect the whole body. The oral-systemic link describes the tight connection between oral health and systemic disease that is now well-documented and accepted by researchers and clinicians around the world. Gum disease increases the risk of preterm birth, Alzheimer’s,11 heart disease,12 head and neck cancers,13 rheumatoid arthritis,14 and lung infections.15,16


Treatments for Leaky Gut

You may wonder, “how is leaky gut treated?” It starts with improving overall gut health. Before taking supplements for leaky gut, your practitioner will want to get rid of any gastrointestinal infections, boost the friendly bacteria in your gut, and improve digestion with enzymes.

Diet plays a big role in healing leaky gut. Avoiding certain foods can give the gut lining a chance to rest and heal. A healthy, whole food, plant-based diet nourishes a healthy microbiome and gut lining. It calms down inflammation in the gut. A gluten-free diet can decrease intestinal permeability and zonulin levels right away.

Once these foundational areas have been addressed, it’s time to heal the gut lining.

There are many leaky gut supplements3 that calm down inflammation, soothe the irritated gut tissue, and seal up holes in the leaky gut. These supplements usually contain a few specific ingredients: L-glutamine, aloe, deglycyrrhizinated licorice (DGL), and soothing herbs for the gut lining. Choose high-quality, professional line supplements. A few leaky gut supplements that I like and recommend are G.I. Benefits, GI Revive, and Glutagenics.

L-Glutamine is important for many functions in the body and is an extremely popular leaky gut supplement. It is an amino acid used as a fuel source for cells in the gut and mouth lining. Glutamine can help gut lining (epithelial) cells heal and improve their connections to neighboring cells. That makes the barrier stronger and healthier.

Slimy and slippery herbs such as slippery elm and okra. The gut lining is covered in mucus or snot. Lovely, right? Sometimes adding more slippery and slimy botanicals can give the gut lining what it needs for protection and to allow it to heal. DGL is another slimy and soothing herbal component from licorice that coats and protects the gut lining so it can slowly heal itself.

Aloe vera is often included in leaky gut supplements to calm down inflammation and soothe the gut lining.

Probiotics are an important supplement for leaky gut. They encourage good bacteria to grow, calm down the angry immune system, and generally promote healthier gut function. Probiotics can crowd out pathogenic bad bacteria. They improve regularity, a more comfortable gut, and ward off diarrhea.

Vitamins promote a strong gut barrier that resists infection and heals more quickly. B vitamins, zinc, and vitamin A are just a few of the nutrients that can build up a healthy gut lining. A high-quality multivitamin-mineral is a must-have to make sure your gut lining has everything it needs to heal.


Test for Leaky Gut and Address Systemic Inflammation

Leaky gut can set you up for inflammation and an angry, confused immune system. By treating leaky gut, clinicians and consumers can turn off inflammation and reverse chronic illnesses. Autoimmune diseases, cancer, depression, diabetes, irritable bowel syndrome, and obesity are believed to be exacerbated or caused by leaky gut. Leaky gut tests make it possible for practitioners and patients to figure out if leaky gut is at the root cause. Some leaky gut tests are available only to providers while others can be purchased by the consumer. Whether you drink a lactulose-mannitol solution before a urine test or get a blood draw will factor into what test is best for you.

Treatments for leaky gut include soothing, healing, and nutrition-boosting supplements. Once leaky gut is improved, the immune system calms down and starts to behave again. Inflammation decreases, so symptoms start to fade away. Lab results return to normal. Autoimmune diseases like rheumatoid arthritis and psoriatic arthritis will see improvements in pain, swelling, and joint stiffness. Medications can be reduced. When leaky gut is fixed, it breaks the cycle of chronic inflammation. You can do the things you love, be more active, and feel like your old self again.



Precision Point Diagnostics is an innovator of testing solutions that assist in the diagnosis and management of conditions commonly addressed by integrative & functional medicine. Our unique profiles are designed to help practitioners address comprehensive approaches to patient care.



  1. Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Research. 2020;9doi:10.12688/f1000research.20510.1
  2. Fasano A. Leaky gut and autoimmune diseases. Clinical reviews in allergy & immunology. Feb 2012;42(1):71-8. doi:10.1007/s12016-011-8291-x
  3. Aleman RS, Moncada M, Aryana KJ. Leaky Gut and the Ingredients That Help Treat It: A Review. Molecules. Jan 7 2023;28(2)doi:10.3390/molecules28020619
  4. Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. Jul 28 2023;doi:10.1007/s11739-023-03374-w
  5. Di Tommaso N, Gasbarrini A, Ponziani FR. Intestinal Barrier in Human Health and Disease. International journal of environmental research and public health. Dec 6 2021;18(23)doi:10.3390/ijerph182312836
  6. Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut. Aug 2019;68(8):1516-1526. doi:10.1136/gutjnl-2019-318427
  7. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. May 2007;85(5):1185-96.
  8. Corazza GR, Falasca A, Strocchi A, Rossi CA, Gasbarrini G. Decreased plasma postheparin diamine oxidase levels in celiac disease. Digestive diseases and sciences. Aug 1988;33(8):956-61.
  9. Schmidt WU, Sattler J, Hesterberg R, et al. Human intestinal diamine oxidase (DAO) activity in Crohn’s disease: a new marker for disease assessment? Agents and actions. Apr 1990;30(1-2):267-70.
  10. Park DY, Park JY, Lee D, Hwang I, Kim HS. Leaky Gum: The Revisited Origin of Systemic Diseases. Cells. Mar 23 2022;11(7)doi:10.3390/cells11071079
  11. Kamer AR, Pushalkar S, Gulivindala D, et al. Periodontal dysbiosis associates with reduced CSF Abeta42 in cognitively normal elderly. Alzheimers Dement (Amst). 2021;13(1):e12172. doi:10.1002/dad2.12172
  12. Bale BF, Doneen AL, Vigerust DJ. High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis. Postgrad Med J. Apr 2017;93(1098):215-220. doi:10.1136/postgradmedj-2016-134279
  13. Mascitti M, Togni L, Troiano G, et al. Beyond Head and Neck Cancer: The Relationship Between Oral Microbiota and Tumour Development in Distant Organs. Frontiers in cellular and infection microbiology. 2019;9:232. doi:10.3389/fcimb.2019.00232
  14. Araujo VM, Melo IM, Lima V. Relationship between Periodontitis and Rheumatoid Arthritis: Review of the Literature. Mediators of inflammation. 2015;2015:259074. doi:10.1155/2015/259074
  15. Zemedikun DT, Chandan JS, Raindi D, et al. Burden of chronic diseases associated with periodontal diseases: a retrospective cohort study using UK primary care data. BMJ open. Dec 19 2021;11(12):e048296. doi:10.1136/bmjopen-2020-048296
  16. Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim). Apr-Jun 2017;11(2):72-80.

Cass Nelson-Dooley, M.S.

Cass Nelson-Dooley, M.S.

Cass Nelson-Dooley, MS, is a researcher, author, educator, and laboratory consultant. She studied medicinal plants in the rain forests of Panama as a Fulbright Scholar and then launched a career in science and natural medicine. Early on, she studied ethnobotany, ethnopharmacology, and drug discovery at the University of Georgia and AptoTec, Inc. She joined innovators at Metametrix Clinical Laboratory as a medical education consultant helping clinicians use integrative and functional laboratory results in clinical practice. She owns Health First Consulting, LLC, a medical communications company with the mission to improve human health using the written word. Ms. Nelson-Dooley is an oral microbiome expert and author of Heal Your Oral Microbiome. She was a contributing author in Laboratory Evaluations for Integrative and Functional Medicine and Case Studies in Integrative and Functional Medicine. She has published case studies, book chapters, and journal articles about the oral microbiome, natural medicine, nutrition, laboratory testing, obesity, and osteoporosis.