Guest Post By Dr. Fiona McCulloch, BSc ND

It’s more than likely that you’ve already heard of the term “leaky gut” before. It’s a condition that naturopathic doctors have talked about for years, but the traditional medical community has always discounted it. With new information coming to light over the past few years, however, we now have scientific evidence that leaky gut, now known as intestinal permeability, does exist. So, what exactly is leaky gut, you ask?

Your small intestine is where the majority of nutrient absorption takes place. This 22-foot length of intestine is far more than a simple tube; it’s a complex system where many different biochemical reactions take place so that nutrients from the food we consume can enter into the body. This intestine is composed of 3 main sections: the duodenum, jejenum, and ileum. As foods are introduced into the digestive tract, stomach acid, bile and pancreatic enzymes will break the food down so they are small enough to absorb.

The “lining” of the small intestine and how it becomes leaky

The inside of the small intestine is covered in columns of epithelial cells, which are organized into folds known as “villi”. These cells act as a barrier that prevents the contents of the intestine from entering directly into the body, and the villi increase the surface area for absorption. Microscopic finger-like pieces of tissue—the microvilli—stick out from the villi, and selectively draw nutrients into the bloodstream Tiny particles including certain forms of amino acids, free fatty acids, vitamins, minerals, oligosaccharides and simple sugars can enter the bloodstream through the capillaries and lymphatic vessels of the tiny microvilli.

Along the surface of the small intestine, the individual epithelial cells are lined up directly side-by-side. Where the cells rest up against each other is known as the “tight junction”. This junction serves as a permanent barrier to toxins, undigested foods and microorganisms that are present in the intestine, any of which could be harmful if they entered into the bloodstream. Although the tight junction is supposed to be impenetrable, research in recent years has determined that this might not actually be so.

Dr. Alessio Fasano is a world-renowned researcher who studies the mechanisms of autoimmune disorders including celiac disease (an autoimmune response to gluten), and other-gluten-related disorders.

Through Dr. Fasano’s research, a new molecule, zonulin was discovered. Zonulin is the only known protein that regulates the tight junctions between the intestinal cells. When it is released in increasing or excessive amounts, these junctions open and allow the contents of the intestine to enter, escaping the intensive filtration of the microvilli.

So why is this a problem?

Consider this: directly beneath the small intestinal epithelial cells lies one of the largest concentrations of lymphoid tissue (immune tissue) in the entire body, known as the GALT (Gut Associated Lymphoid Tissue). This is where immature cells of the immune system grow and mature. As such, when particles such as foods, environmental toxins, and microbes are allowed to pass through the intestine freely as they do as a result of a “leaky gut”, the immune cells may not develop normally in response to these influences. It’s also clear that when particles come into direct contact with the immune cells, they activate the immune response, creating an inflammatory state in the body. Evidence is also coming to light that leaky gut plays a key role in the development of autoimmunity, possibly by disrupting the ability of immune cells to tolerate “self” tissues as they go through their crucial stages of early development in the GALT.

What causes zonulin release, exactly? How does the gut become leaky?

It’s now known that when the intestinal epithelial cells are exposed to gliadin (a component of gluten), they will release zonulin, whether the person has celiac disease or not[1]. In a patient who has celiac disease, this release provokes an autoimmune reaction so intense that it takes a very long time for the intestine to recover. In those without celiac disease, the recovery takes far less time. Different individuals have different abilities to recover from this gliadin exposure.

Other factors involved in creating leaky gut may include dysbiosis and microbial imbalances[2], candida[3], toxins and inflammation[4], food allergies[5], or anything that irritates the intestinal epithelial cells.

How does leaky gut relate to PCOS?

Interestingly, leaky gut may aggravate women with PCOS in a variety of different ways: for example, a 2010 study found that women with PCOS had an increased likelihood of irritable bowel syndrome (IBS)[6]. IBS is often often used to describe irregular intestinal function, bloating and discomfort, but many integrative doctors have found that it correlates well with leaky gut. The same study found that the women with IBS were also more likely to have a higher body mass index and body fat percentage . As we all know so well, obesity affects women with PCOS in great numbers, and is strongly correlated with insulin resistance and hormonal imbalance in the condition. It appears that there is in fact an emerging link between obesity and leaky gut [7].

In recent years, researchers are also learning that there is a definite autoimmune connection in PCOS.

It’s been known for some time that women with PCOS are at increased risk for Hashimoto’s thyroiditis[8]; an autoimmune condition of the thyroid gland. Having impaired thyroid function will aggravate the metabolic markers in PCOS, creating further hormonal imbalance. It’s also known that women with PCOS have genetic polymorphisms that predispose them to increased inflammation.

More recently, there is some evidence that increased autoimmune activation between the adrenals and ovaries may be involved in the high amount of male hormones in PCOS[9]. The ovary has been described as an immunological hotspot, and a dysfunctional immune system has been found to disrupt a variety of different hormonal processes in the body[10].

For women with PCOS who are trying to conceive, the relationship is even clearer: an overactive immune system, including conditions such Hashimoto’s thyroiditis, and increased amounts of various inflammatory markers, are linked to recurrent miscarriage and infertility[11].

To go back into general health, leaky gut is linked to the malabsorption of key nutrients such as vitamin A, magnesium, zinc, vitamin D, and calcium[12]. When key nutrients are not properly assimilated, conditions that are common in women with PCOS may be aggravated, such as anxiety and depression, inflammation, and fatigue.

What is the treatment for leaky gut?

There are a few steps that you can take that will greatly improve your intestinal health and allow the intestinal barrier to heal.

The 4 R program as listed below is often used by clinicians to repair leaky gut and restore intestinal health, but keep in mind that these types of programs are best supervised by a licensed practitioner, as patients may have very different needs for each stage of the program.

1) Remove:

Remove any irritating foods. Removing gluten from your diet is key, knowing that it causes zonulin release and aggravates leaky gut. Removing allergenic foods, gastric irritants such as alcohol, and NSAIDS like ibuprofen is also advisable. Another important step in the “remove” stage is the killing of candida or other microbes that may be overgrowing in the intestine, which may be done with a variety of natural compounds.

2) Replace:

Replace either hydrochloric acid if low stomach acid is an issue, and/or digestive enzymes if there are difficulties digesting foods. This encourages the proper breakdown of the foods that travel through the intestine. Ask your naturopath or clinician if you have the symptoms of either of these deficiencies and then replace accordingly.

3) Re-inoculate:

During this stage, beneficial bacteria—also known as probiotics—are supplemented. It’s important to note that not all probiotics are made the same way: different strains may have completely different effects. I often use special combinations of anti-inflammatory probiotic strains in my practice to reduce autoimmune and inflammatory responses in women with PCOS.

4) Repair:

During this stage, nutrients that heal the intestinal lining and calm inflammation in the gut may be recommended. These nutrients can include a wide variety of different compounds such as calcium d-glucarate, slippery elm, L-glutamine, NAC, DGL and many others, depending on the patient and their presentation.

If you have PCOS, it’s important to remember that your intestine is the first entry point for the nutrients that your body needs to function, and that a healthy gut is the foundation through which your immune system develops. Without a healthy gut, the response to other treatments for PCOS may not be as optimal. A healthy intestine sets the stage for good nutrient absorption, a healthy immune system, reduced inflammation, and better metabolic health, so do your best to focus in on this key area of your body and show your gut some love!

Dr. Fiona McCulloch is a board certified Naturopathic Doctor who has been in practice for 13 years in Toronto, Canada. She graduated with aBachelor of Science degree (Biological Sciences) from the University of Guelph and went on to graduate from the Canadian College of Naturopathic Medicine. She is the founder and owner of White Lotus Integrative Medicine , a busy clinic specializing in women’s health and fertility. Her clinical focus is on the treatment of a wide range of fertility and hormonal conditions, and she is an avid writer and researcher, having published articles in major naturopathic journals. Fiona has been able to reverse her own PCOS with natural methods and is thrilled to be able to share what she has learned with other women suffering through the same concerns. Her first book: 8 Steps to Reverse Your PCOS is now available. She lives in Toronto with her husband and 3 boys.





[1] Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19. [2] Martin-Villa JM. Neuroendocrine Stimulation Of Mucosal Immune Cells In Inflammatory Bowel Disease. Curr Pharm Des. 2014 Jan 30. [3] Yan L, Yang C, Tang J. Disruption of the intestinal mucosal barrier in Candida albicans infections. Microbiol Res. 2013 Aug 25;168(7):389-95. doi: 10.1016/j.micres.2013.02.008. Epub 2013 Mar 30. [4] Catalioto RM, Maggi CA, Giuliani S. Intestinal epithelial barrier dysfunction in disease and possible therapeutical interventions. Curr Med Chem. 2011;18(3):398-426. [5] Järvinen KM, Konstantinou GN, Pilapil M, Arrieta MC, Noone S, Sampson HA, Meddings J, Nowak-Węgrzyn A. Intestinal permeability in children with food allergy on specific elimination diets. Pediatr Allergy Immunol. 2013 Sep;24(6):589-95. [6] Mathur R, Ko A, Hwang LJ, Low K, Azziz R, Pimentel M. Polycystic ovary syndrome is associated with an increased prevalence of irritable bowel syndrome. Dig Dis Sci. 2010 Apr;55(4):1085-9. [7] Teixeira TF, Collado MC, Ferreira CL, Bressan J, Peluzio Mdo C. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res. 2012 Sep;32(9):637-47. [8] Kachuei, M., Jafari, F ., Kachei, A. & Keshteli, A. H. Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Arch. Gynecol. Obstet. 285, 853–856 (2012). [9] Gleicher, N. et al. Is [9] Gleicher, N. et al. Is androgen production in association with immune system activation potential evidence for existence of a functional adrenal/ovarian autoimmune system in women? Reprod. Biol. Endocrinol. 11, 58 (2013). [10] De Bellis, A., Bizzarro, A., Pivonello, R., Lombardi, G. & Bellastella, A. Prolactin and autoimmunity. Pituitary 8, 25–30 (2005). [11] Carp, H. J., Selmi, C. & Shoenfeld, Y . The autoimmune bases of infertility and pregnancy loss. J. Autoimmun. 38, J266–J274 (2012).