What is Intestinal Permeability or "Leaky Gut"?

What is intestinal permeability or “leaky gut”? Why haven’t I heard of this?  Intestinal permeability causes systemic inflammation.  Intestinal permeability as a precondition for the development of autoimmune disease.

This is part 1 of a 5-part series on Intestinal Permeability (Leaky Gut)

Main points of this issue

  • What is intestinal permeability (or leaky gut)?
  • Intestinal permeability causes systemic inflammation
  • Leaky gut syndrome is very real
  • Research on Intestinal Permeability/Leaky Gut Syndrome
  • Why haven’t I heard of this?
  • Health Conditions Associated with Leaky Gut Syndrome
  • Intestinal permeability as a precondition for the development of autoimmune disease?

Most people know that one of the primary functions of the gastrointestinal (GI) tract is to break down large macromolecules ingested as food into small micronutrients which are then absorbed through the intestinal lining and enter the bloodstream. These micronutrients then serve as fuel sources for the body. However, many people dont know that the intestinal lining also serves another important function: it acts as a barrier and prevents the absorption of large molecules into the bloodstream, such as undigested protein, bacteria and toxins.

These large molecules should pass through the entire GI tract and be eliminated from the body without being absorbed and entering the bloodstream. This barrier function is a very important function of the epithelial lining of the GI tract. If the intestinal barrier starts to become too permeable and “leak”, this may pose many problems for the body.

Intestinal permeability will cause systemic inflammation

If anything penetrates through this gastrointestinal barrier that is foreign, the immune system is activated to eliminate or destroy these unwelcome molecules. This activation of the immune system leads to an inflammatory response. If you look at the anatomy of the intestinal lining, it is mostly immune cells with a thin layer of epithelial cells protecting it. If that layer gets breached, there is no question there will be an inflammatory immune response. So it is no surprise to see systemic inflammation and autoimmunity when there is breach of this thin epithelial lining.

If a person has their barrier system breached, they will have an increase in inflammatory response. Increases in inflammatory responses increase risk of all chronic disease, including depression and neurodegenerative diseases, cardiovascular disease, bone loss, autoimmune disease, inflammatory bowel disease and chronic pain. A persons intestinal barrier integrity will influence their inflammatory load and their potential for deteriorating mechanisms throughout the body.

Is “Leaky Gut” real?

Is leaky gut a myth, like Bigfoot, or is it real? Leaky gut syndrome is very real. The immunological literature is filled with information on leaky gut syndrome. This topic has been getting more and more attention in the literature over the past 5 to 10 years. In the immunological literature, leaky gut syndrome has been linked to autoimmunity, depression, congestive heart failure and neurodegenerative disease of all types.

Research on Intestinal Permeability/Leaky Gut Syndrome

There has been an explosion of research on leaky gut syndrome in the past 10 years. Researchers have been able to identify the messenger protein (called zonulin) that leads to leaky gut. They have been able to purify the peptide and induce leaky gut with zonulin exposure in animal models. Now they have the clinical ability to induce leaky guts in animals. One of the interesting things that has been shown in animal models is the induction of autoimmune disease, such as type I (juvenile-onset) diabetes, immediately, by inducing leaky gut!

Why haven’t I heard of this?

Most people in the conventional world don’t know about leaky gut syndrome or intestinal permeability. Why? Because there is no drug currently available to treat it so most doctors have not heard of it. This will change shortly because drug companies are now working on a leaky gut drug. Once they develop the drug, everyone will know about it.

There is now a zonulin-blocker (called Z-100) being developed which they have given to animals and this has drastically decreased their intestinal inflammation. Zonulin is one of the peptide messengers that leads to leaky gut syndrome. In animal studies, they have been able to block zonulin and stop leaky gut. Once these drugs have been tested on humans and we have a human zonulin-blocker, everyone in the world will be looking for leaky gut.

Health Conditions Associated with Leaky Gut Syndrome

The following conditions have been associated with leaky gut syndrome:

  • Autoimmune disorders
  • Multiple food sensitivities
  • Multiple chemical sensitivities
  • Chronic fatigue syndrome
  • Heart failure
  • Depression
  • Chronic inflammatory conditions
  • Chronic pain
  • Inflammatory bowel
  • Chronic yeast overgrowth syndromes
  • Brain fog

Intestinal Permeability and Autoimmune Disease

There is a growing amount of evidence establishing the connection between intestinal permeability and the development of autoimmune disease.

This review paper was published in 2009 in the Annals of New York Academy of Science. This journal is one of the top-rated most powerful scientific journals available:

“There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases. Therefore, we hypothesize that loss of intestinal barrier function is necessary to develop autoimmunity.”1

Basically, what this paper is saying, is that the research is pointing to intestinal permeability, or leaky gut, as a precondition for the development of all autoimmune disease, such as type I diabetes, rheumatoid arthritis, lupus, Hashimotos, Graves, Crohns disease, ulcerative colitis, Celiac disease, etc.

Here’s another paper supporting this discovery:

“Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. When the finely-tuned trafficking of macromolecules is dysregulated in individuals, both intestinal and extraintestinal autoimmune disorders can occur.”2

One of the things we have to have in order to prevent autoimmune disease is immune tolerance to self-tissue. This prevents our immune system from attacking ones own tissue of the body. One of the things they are finding is once these tight junction proteins get compromised, there is such immune zealousness and activation, this whole immune self-tolerance is lost and the immune system is prone to attacking self-tissue. When this occurs, any tissue is up for grabs for autoimmune destruction. The type of tissue that is targeted for destruction determines the type of autoimmune disease that develops.

Content provided by Datis Kharrazian, D.C., Breaking the Complex Web of Leaky Gut Syndrome, 2/10/11

In part 2 of this 5-part series, we answer the following questions:

  • What chronic diseases have been associated with intestinal permeability?

Continue to part 2 of series

1. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205
2. 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