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Intro to “leaky gut” – what it is and why you should care

Today’s post is brought to you by Dr. Alexandra Perreiter, PharmD of She is also a clinical pharmacist who I recently connected with. I hope you enjoy her post and check out her site!

Even though all health care professionals have taken the Hippocratic Oath of “First do no harm,” little did we learn in our professional schools regarding Hippocrates’s philosophy on treating and preventing disease, including his famous quote “Let food be thy medicine and medicine be thy food.” This is unfortunate because while conventional medicine is superb in diagnosing disease, little attention is being placed on identifying and targeting the actual root causes of these diseases to prevent them from occurring in the first place.

Currently the prevailing theory regarding the cause of many chronic diseases is genetics. Unfortunately, this theory alone appears insufficient to explain our susceptibility towards disease, especially because it is undeniable that many chronic diseases, such as autoimmune diseases and chronic pain syndromes are much more prevalent in the developed world than the undeveloped world. Take, for example, Japanese women who come to live in the United States. While their risk of developing breast cancer is quite low when they live in Japan, once they move to the United States their risk increases dramatically.[i] Why? It is definitely not because their genes have changed. Instead it is because their gene expression has changed, which is largely dictated by the environment (a field referred to as epigenetics).[ii],[iii] Thus, if we can understand what environmental factors turn on and off gene expression, we might be able to prevent disease and/or restore health.

And this is where we are starting to comprehend what Hippocrates had already eluded to many centuries ago, namely that “all disease begins in the gut.”[iv]

But why just is our gut so important?

Mainly because everything we take in from the external environment passes through our gut and, thus, our gut needs to finely regulate what actually passes from our gastrointestinal (GI) tract into our blood stream and from there into our organs, tissues and cells.

This is why our body has created a very finely tuned “gut-blood barrier” that determines what will or will not enter our body. We need this barrier (aka the “intestinal epithelial lining”) to function properly, only allowing “good things” (like nutrients) to enter and “bad things” (like disease causing bacteria) to stay out.[iii]This is, for example, one reason why ~70-80% of our immune system lies in our gut (referred to as the gut-associated lymphoid tissue (GALT), which houses plasma cells, mainly Immunoglobulin A (IgA), which provide first line defense to foreign invaders).[v]

So what then affects this “intestinal permeability”? The long answer is many things, including antibiotics, toxins, stress and infections.[iv]However, the two major factors that appear to be the most commonly cited and perhaps most modifiable are: 1) food and 2) the bacteria that live in our gut (aka “microbiome”).[iv],[vi],[vii] And these two factors are interrelated in that the food we eat can help or hinder bacteria to live in our gut and, vice versa, bacteria in our gut can give us “food cravings” that can then promote certain bacteria to thrive and others to die. We now know that roughly 39 trillion bacteria (400 different species!) live in our body – which is about the equivalent to all human cells in our body combined![iv],[viii],[ix] Thus, it is important that we understand that our gut bacteria play a crucial role in our overall health and look at food not only in its relationship to micro- and macronutrients, but also in its relationship to cause this excessive “intestinal permeability”, also referred to as “leaky gut”.

One of the major proteins known to increase the “holes” in our gut lining is zonulin.[iii],[vii],[x] It does so by causing a dysregulation of our “tight junctions”, thereby allowing things to enter our body that were never intended to be present. We now have pretty good evidence to suggest that overexpression of zonulin seems to be associated with autoimmune diseases (like rheumatoid arthritis and multiple sclerosis), neurodegenerative diseases (like dementia and Alzheimer’s disease), psychiatric diseases as well as cancer development and inflammatory diseases (such as Type 2 diabetes)![iii],[xi],[xii],[xiii] Overexpression of zonulin has been specifically associated with certain types of foods, such as gluten.[vii] However, enteral infections can also contribute as can other things that change our microbiota (such as medications that can alter the pH of our stomach, etc.)[iv]

So, how then does this “leaky gut” ultimately lead to chronic disease? In essence what happens is that things (in particular large protein particles) start entering our body that were never meant to get out of our intestine. These things are registered as foreign by our body, so our body goes on defense mode and starts mounting an immune response to protect ourselves from the “bad guys”. Unfortunately, the leakier our gut, the more “bad guys” are coming in and the harder our immune system fights. Even worse, the “bad guys” that our immune system should have never seen (had we had a better gut barrier) look so similar to our own cells that as the assault continues, our body starts attacking our own cells thinking they are “bad guys”. This confusion is called “molecular mimickry“ and may be the root cause of many chronic diseases that are on the rise. But this isn’t where it stops.[xiv]

On a normal day and in a normal person, a small percentage of our cells die off and get replaced with new ones. To do so our body generates a small amount of autoantibodies (aka “antibodies against self”) that help get rid of the damage. However, when we have a large amount of cellular damage on a consistent basis as a result of molecular mimickry, we end up developing more and more autoantibodies to get rid of all the cellular damage and then, after a while, our autoantibodies get so overwhelmed and confused that they autoperpetuate, resulting in more and more inflammation and damage that ultimately results in us developing a chronic disease.[xiv]

Thus, in essence, so the theory goes, most chronic diseases are caused by mis-regulation of our immune system that in one way or the other is misguided by environmental triggers. While leaky gut may not be the only reason why these diseases develop, many do believe it to be the main contributor and that fixing our “leaky gut” and restoring normal intestinal permeability will prevent and may even reverse such chronic diseases and cause disease remission.[xv]

So, what can we do? While research is ongoing into ways to restore and maintain a healthy gut-blood barrier, here are some things that health care professionals are already doing[iv] (Note: The below is not to be misconstrued as medical advice. You should be under medical supervision before you try any of the below mentioned options, including, but not limited to, the supplements listed. As with any lifestyle changes, you should always consult your healthcare provider before undergoing them and be monitored throughout the process.):

  • An Elimination diet.[iv],[xiv] Elimination diets usually consist of avoidance of all of the potential food causes, such as gluten, dairy, legumes, etc., for 14 – 30 days, followed by reintroduction of the food groups one after the other to determine which ones may affect you. This can be a very challenging process, but it can also be extremely rewarding because symptoms one has been having for years may suddenly disappear.
  • Strict whole food diet, with complete elimination of processed foods, including highly refined carbohydrates and vegetable oils as well as artificial coloring, sweeteners and preservatives.[iv],[xiv]
  • Supplementation with a probiotic with at least 50+ billion colony-forming units and containing Lactobacillus and Bifidobacterium[xvi] Quality brands include OrthoMolecular, Klaire Labs, and Pure Encapsulations.*
  • Bone brothiv and other glycine rich containing foods. (Thrive Market has a variety of options including Kettle & Fire (my favorite), or you can make your own, and/or supplement with Collagen Protein like Vital Proteins)
  • Colostrum[xvii](OrthMolecular’s IGG Protect or Tegricel Colostrum by Designs for Health are good options*)
  • Glutamine[vi](Thorne Research, PureEncapsulations and others have glutamine, it’s also an ingredient in GI Revive by Designs for Health as well as GI Repair Powder by Vital Nutrients*)
  • Stress management[iv] (including plenty of sleep!)

*You can find these supplements on Full Script under Gut Health.

Dr. Perreiter

**this post contains affiliate links to products Dr. Hartzler recommends, all the supplements recommended in this post can be found in my FullScript Store You do have to set-up a quick account to use.  Thanks for supporting the blog, remember 10% goes to support various ministries! Check out My Favorite Things for more details. Reminder that this information is general and personal specific health decisions should be made between you and your medical provider. Remember supplements can interact with certain medications, so make sure to include a pharmacist knowledgeable in this area in your decisions as well.

[i] Dunn JE. Breast cancer among American Japanese in the San Francisco Bay area. Natl Cancer Inst Monogr. 1977 Dec;47:157-60.

[ii] What is Epigenetics (2017, July 23). Epigenetics: Fundamentals. Retrieved from

[iii] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.

[iv] Kresser, C. (2011, February 24). 9 Steps to Perfect Health – #5: Heal Your Gut. Retrieved from

[v] Vighi G, Marcucci F, Sensi L, Di Cara G, Frati F. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008 Sep; 153(Suppl 1): 3–6.

[vi] Rapin JR, Wiernsperger N. Possible links between intestinal permeability and food processing: a potential therapeutic niche for glutamine. Clinics (Sao Paulo). 2010 Jun;65(6):635-43.

[vii] Hollon J, Puppa EL, Greenwald B, et al. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015 Feb 27;7(3):1565-76.

[viii] Gill H.S., Guarner F. Probiotics and human health: A clinical perspective. Postgrad Med J. 2004;80:516–526.

[ix] Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016 Aug:14(8):  e1002533.

[x] Fasano, A. Intestinal Permeability and its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-1100.

[xi] Kelly JR, Kennedy PJ, Cryan JF, et al. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015; 9: 392.

[xii] Galland L. The gut microbiome and the brain. J Med Food. 2014 Dec 1; 17(12): 1261–1272.

[xiii] Mu Q, Kirby J, Reilly CM, et al. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017; 8: 598.

[xiv] O’Bryan T. (2016). The Autoimmune Fix. New York, NY: Rodale Inc.

[xv] Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22.

[xvi] Chutkan, R. (2015).The Microbiome Solution. New York, NY: Penguin Random House LLC.

[xvii] Hałasa M, Maciejewska D, Baśkiewicz-Hałasa M, et al. Oral supplementation with bovine colostrum decreases intestinal permeability and stool concentrations of zonulin in athletes. Nutrients. 2017 Apr; 9(4): 370.

2 thoughts on “Intro to “leaky gut” – what it is and why you should care

  1. […] factors alone. Research has demonstrated that food allergy, defects in the gut mucosal barrier (ie leaky gut), and increased intestinal permeability may play a role in the development of eczema.3 Dietary […]

  2. […] foods to aid in relieving digestive symptoms that are not related to bacterial imbalance. See this link to read a previous Pharm To Table blog post discussing the effects of diet on gut […]

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