understanding intestinal permeability

what is leaky gut? 

‘Leaky’ gut, or increased intestinal permeability (the medical name for leaky gut), is a condition that occurs when the lining of the gut becomes inflamed or damaged and fails to act as an effective barrier. It allows substances from inside the gut to move through the gut wall into places that they shouldn’t be.

Our gut is essentially one long tube, from the mouth to the anus, lined by a membrane (called the gut epithelium) that is just one cell thick. That lining looks different in different areas. In the intestines, for example, these cells have finger-like projections at the top, called villi. The membrane cells sit next to each other in a long row. In a healthy gut, the junctions between them are tight, to only selectively allow substances to pass through (like a security checkpoint!). In a leaky gut, the gut lining cells become inflamed or damaged and the tight junctions between them become loose, stopping them from being effective gatekeepers and allowing microbes, toxins and other substances to pass through.

 

how does a leaky gut develop?

The epithelium of the gut has several mechanisms to keep it healthy. It secretes a layer of mucus to ‘coat’ the epithelium, and it also has special proteins forming the junctions between the cells, holding them tightly together – these act a bit like tightly pulled shoelaces. Zonulin is one of the proteins that help to regulate these tight junctions.

There is a lot of evidence that the gut microbiome (the trillions of microorganisms occupying the gut and that help support the gut epithelium) secretes chemicals and proteins that can either provide nutrients to support the strength of the mucus layer, or secrete inflammatory chemicals that damage the gut epithelial cells¹. The gut immune system sits on the other side of these epithelial cells. It can become activated or damaged by toxins, increasing issues with the production of inflammatory chemicals.

Conversely, many of the gut heroes that we discuss have been shown to help heal a leaky gut. Dysbiosis (disruption of the microbiome) is one of the main factors that contribute to leaky gut (and prevents it from resolving). Stress, infection, inflammation, toxins and medications are other common causes.

Recent evidence shows that vitamin D has a role in regulating the opening and closing of the tight junctions between the guts’ epithelial cells.² We also know that colostrum, which is secreted in the first few days that a new mother produces breast milk, acts on the baby’s gut to tighten these junctions between the cells³ – yet another reason to strongly support breastfeeding.

Wheat is thought to be a trigger to intestinal permeability in those who have coeliac disease (an allergy to gluten), wheat allergies and those who experience symptoms with wheat consumption (non-coeliac wheat sensitivity). A breakdown in the gut lining has been seen in all three conditions.⁴ Animal studies show that wheat may be a contributing agent to intestinal permeability in many diseases and possibly even in asymptomatic individuals.⁵

 

how could leaky gut affect me?

When the gut wall becomes leaky, as well as microbes, it can also allow undigested  food particles to pass through. In a healthy gut, only small food particles broken into their constituents are allowed through the gut wall. When a larger particle comes through a leaky gut, the immune system on the other side can identify this as a foreign invader and become primed to react to that ‘food’. This leads to an increased development of food allergies and intolerances in people suffering from a leaky gut, or it can cause inflammation.⁶ Whilst excluding that particular food can be helpful for symptoms, it is important to heal the gut to prevent more food reactions from occurring.

Research over the last 10 years has shown a link between leaky gut and many diseases and conditions such as inflammatory bowel disease (Crohn’s and ulcerative colitis), IBS (irritable bowel syndrome), coeliac disease, obesity and weight gain, diabetes, Alzheimer’s, Parkinson’s, depression and autism.

 

There is also increasing evidence that when intestinal permeability occurs, the inflammatory chemicals circulating in response to this can affect the blood-brain barrier and make this leaky too. Functional and integrative medicine practitioners describe this as ‘leaky gut/leaky brain’. A compromised blood-brain barrier allows through toxins and other inflammatory substances and has been linked to the pathology of Alzheimer’s, Parkinson’s, motor neurone disease, schizophrenia, depression, autism, stroke, epilepsy and other neurodegenerative diseases.⁸ Many patients with digestive issues complain of experiencing brain fog, which resolves, as we work on their gut health.

If you are struggling with digestive symptoms like diarrhoea, constipation, abdominal pain, reflux or indigestion or are suffering from allergies and food reactions, fatigue, anxiety or depression you could have a leaky gut.⁹ You may also wish to have further testing carried out by a functional medicine practitioner.

 

can I test for a leaky gut? 

There are several tests available privately to test for intestinal permeability. There is no one ideal test, but the most reliable intestinal permeability test in Dr Jess’s clinical experience is Cyrex’s Array 2, which measures a range of antibodies that react to products released by a leaky gut. This test is available from Regenerus Labs in the UK, but requires a practitioner to authorise the test for you.

It’s worth noting that with your new understanding of gut health, leaky gut and dysbiosis as the root causes of many diseases, sometimes testing for leaky gut is less important than focusing on the many simple home remedies that you can use to support your gut, without medical intervention.

 

available testing:

zonulin levels. Measured through a stool or blood test

This is the most common test available. Zonulin is the special protein that helps keep the junctions tight between the gut epithelial cells, preventing leaky gut. If zonulin is found in high levels in your blood or stool, then it could suggest a leaky gut.¹⁰ However, there is some daily variability in zonulin levels, which can make this test unreliable.¹¹ It’s also possible to have a leaky gut and not have a raised zonulin. In fact, in some studies, it was only raised in a third of patients.¹² In Dr Jess’s experience, zonulin has often not been raised in some of her patients, yet she strongly suspected that clinically, they were suffering from having a leaky gut.

zonulin antibodies. Blood test (part of the Array 2 test from Cyrex)

When zonulin is released into the blood, your immune system responds by making antibodies. You can measure these antibodies on a blood test. Zonulin antibodies¹³ are considered to be a more accurate measure of intestinal permeability than zonulin levels themselves.

other antibodies. Blood test (also part of the Cyrex Array 2 test)

If you have a leaky gut, other abnormal substances, bacterial toxins and proteins can pass through the gut wall. Your immune system produces antibodies against these, which can be measured in your bloodstream. These include lipopolysaccharides (fragments of the bacterial wall) and actomyosin (another junction protein) IgA. These markers can also be very helpful in diagnosing leaky gut, along with zonulin antibodies.

secretory IgA. Stool test (part of the Genova Diagnostics GI effects test, which also looks at dysbiosis and the microbiome).

Secretory IgA is an important antibody that is in the mucus layer of the gut. It helps the immune system to differentiate between the microbiome and potential pathogens.

A raised secretory IgA in a stool test can suggest issues with the epithelial gut lining, as it suggests infection or inflammation in the gut. Low levels can be seen in inflammatory bowel disease, coeliac disease and when under a lot of stress. Abnormalities in secretory IgA would support a diagnosis of intestinal permeability, if other tests were abnormal.

eosinophilic protein X and calprotectin. Stool test (part of the Genova GI effects test)

These are markers of severe inflammation, particularly likely in Inflammatory bowel disease or severe food allergies.

Raised eosinophilic protein X, or calprotectin levels, are markers that indicate one of the immune cells are releasing proteins and are reacting to inflammation in the gut. They may not be raised in intestinal permeability, but if they are raised then they very strongly suggest leaky gut. This would require further investigation with a medical professional, to rule out inflammatory bowel disease.

 

why doesn’t my doctor know about leaky gut? 

For a long time, leaky gut was said to be a fictitious condition, created by alternative medicine. However, with the explosion of research into the microbiome and over 10,000 published research papers in the last 10 years on intestinal permeability, it is now relatively indisputable that it exists. We are still learning about its causes and its impact on many diseases.

There is a significant lag between evidence and changes in mainstream medicine of  up to 17 years.¹⁴ This is why many websites, including the NHS website, do not acknowledge the existence of leaky gut. Whilst a growing number of progressive healthcare workers are educating themselves in functional medicine, gut health and nutrition, much of the education after medical school is self-guided or taught by pharmaceutical companies. This means that your doctor may not be aware of all the recently published microbiome and intestinal permeability research that is out there. It is also not (yet) a major part of hospital guidelines for the treatment of diseases.

 

healing a leaky gut

We are learning that many of the tried-and-tested home remedies and natural gut supports that are hundreds or even thousands of years old, such as fermented food, plant fibres and herbs can all have positive impacts on the microbiome and gut lining.

Traditional medicines, which were based on observation and understanding of people and individual symptoms didn’t need to understand the microbiome or intestinal permeability, to be able to see the things that commonly worked to help the gut.

We know that early life, stress and medications all have a big role to play in the development of a leaky gut. We also know that a diet that supports the gut lining, including important strains of probiotic bacteria, can help the epithelial cells to heal.

 

q&a

1. How long does it take to repair a leaky gut?

It really depends on the situation. We’re all individuals with different personalities, different health stories, different lives and different guts. There is some evidence that interventions like colostrum can improve markers of intestinal permeability within just 10 days, but many studies look at a timeline of between four to eight weeks. If your gut is continually becoming damaged by dysbiosis, medications or allergic or inflammatory triggers (like gluten), this can also affect results.

2. I am having some issue with my skin, could this be a symptom of a leaky gut?

Yes, surprisingly, your gut is also connected to your skin health. Acne,¹⁵ rosacea,¹⁶ and eczema¹⁷ can all be exacerbated by inflammation in the digestive tract. This has been recognised by integrative medical practitioners for many years, who have highlighted the fact that the skin is one of our pathways of detoxification. If the gut (our main detoxification system) is not functioning well, the body may begin to rely on other pathways like the skin. It is also worth noting that food intolerances (IgG antibody reactions), dysbiosis and leaky gut can be a root cause of skin issues and autoimmune issues (including eczema and psoriasis).

 

references:

1. Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders? Nutrients. 2020;12(4):1082. Published 2020 Apr 14. doi:10.3390/nu12041082
2. Hassanshahi M, Anderson PH, Sylvester CL, Stringer AM. Highlight article: Current evidence for vitamin D in intestinal function and disease Exp Biol Med (Maywood). 2019;244(12):1040-1052. doi:10.1177/1535370219867262
3. Taylor SN, Basile LA, Ebeling M, Wagner CL. Intestinal Permeability in Preterm Infants by Feeding Type: Mother’s Milk Versus Formula  Breastfeed Med. 2009;4(1):11-15. doi:10.1089/bfm.2008.0114
4. Cardoso-Silva D, Delbue D, Itzlinger A, Moerkens R, Withoff S, Branchi F, Schumann M. Intestinal Barrier Function in Gluten-Related Disorders Nutrients. 2019 Oct 1;11(10):2325. doi: 10.3390/nu11102325. PMID: 31581491; PMCID: PMC6835310.
5. de Punder K, Pruimboom L. The dietary intake of wheat and other cereal grains and their role in inflammation Nutrients. 2013 Mar 12;5(3):771-87. doi: 10.3390/nu5030771. PMID: 23482055; PMCID: PMC3705319.
6. Xiao N, Liu F, Zhou G, Sun M, Ai F, Liu Z. Food-specific IgGs Are Highly Increased in the Sera of Patients with Inflammatory Bowel Disease and Are Clinically Relevant to the Pathogenesis Intern Med. 2018;57(19):2787-2798. doi:10.2169/internalmedicine.9377-17
7. Schoultz I, Keita ÅV. The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability Cells. 2020;9(8):1909. Published 2020 Aug 17. doi:10.3390/cells9081909
8. Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV.Blood-Brain Barrier: From Physiology to Disease and Back Physiol Rev. 2019;99(1):21-78. doi:10.1152/physrev.00050.2017
9. Ganda Mall JP, Östlund-Lagerström L, Lindqvist CM, et al. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress? BMC Geriatr. 2018;18(1):75. Published 2018 Mar 20. doi:10.1186/s12877-018-0767-6
10. Stevens BR, Goel R, Seungbum K, et al. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression Gut. 2018;67(8):1555-1557. doi:10.1136/gutjnl-2017-314759
11. Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, Krenn CG, Roth GA. Increased plasma zonulin in patients with sepsis Biochem Med (Zagreb). 2013;23(1):107-11. doi: 10.11613/bm.2013.013. PMID: 23457771; PMCID: PMC3900088.
12. Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, Krenn CG, Roth GA. Increased plasma zonulin in patients with sepsis. Biochem Med (Zagreb). 2013;23(1):107-11. doi: 10.11613/bm.2013.013. PMID: 23457771; PMCID: PMC3900088
13. Vojdani A, Vojdani E, Kharrazian D. Fluctuation of zonulin levels in blood vs stability of antibodies World J Gastroenterol. 2017 Aug 21;23(31):5669-5679. doi: 10.3748/wjg.v23.i31.5669. PMID: 28883692; PMCID: PMC5569281.
14. Kristensen N, Nymann C, Konradsen H. Implementing research results in clinical practice- the experiences of healthcare professionals BMC Health Serv Res. 2016;16:48. Published 2016 Feb 10. doi:10.1186/s12913-016-1292-y
15. Bowe WP, Logan AC. Acne vulgaris, probiotics and the gut-brain-skin axis – back to the future? Gut Pathog. 2011 Jan 31;3(1):1. doi: 10.1186/1757-4749-3-1. PMID: 21281494; PMCID: PMC3038963.
16. Weiss E, Katta R. Diet and rosacea: the role of dietary change in the management of rosacea. Dermatol Pract Concept. 2017;7(4):31-37. Published 2017 Oct 31. doi:10.5826/dpc.0704a08
17. eddel, S., Del Chierico, F., Quagliariello, A. et al. Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture. Sci Rep 9, 4996 (2019). https://doi.org/10.1038/s41598-019-41149-6