What Is a Leaky Gut

In short, a leaky gut is a permeable gut. Another buzzword you might run across is intestinal hyperpermeability.

Meaning that what’s on the inside can leak outside.

My own basic understanding is that a normal gut lining is composed of epithelial cells with tight junctions that create a physical barrier. These cells also have a mucosal coating that also functions as a barrier while still allowing the ability to absorb nutrients.

Tight Junctions are one of the ways in which at a cell are attached or separated from the next cell.

Epithelial cells, in part, are held together by the Claudins family of proteins. Claudins are an important part of these tight junctions.

Tight junctions establish the cellular barrier that controls the flow of molecules in the spaces between intestinal epithelial cells.

Zonulin is a protein that modulates the permeability of tight junctions between epithelial cells.

References:
Biology pages: Tight Junctions
Wikipedia: Tight Junctions
Wikipedia: Claudin

Of course, this is a very simple view on what is a leaky gut.

There is much more going on with a healthy gut lining then these few sentences.

Within this environment we just described is our own microbiome. The microbiome is the symbiotic and diverse community of microorganisms that help to digest fiber, extract nutrients, produce vitamins, and provide 80 percent of our immune system.

This is what we know about. What about those unknown unknowns on what is a leaky gut?

Science has just begun to understand the role of our microbiome.

An imbalance of this microbiome community is called dysbiosis. Does a leaky gut cause dysbiosis, or is a leaky gut a result of dysbiosis? Maybe both are correct? Maybe neither is correct?

We’re going to try to fix it all.

This intestinal barrier prevents what’s inside from leaking into the body and bloodstream causing inflammation and an immune response.

What Causes a Leaky Gut

You don’t wake one day with a leaky gut. A leaky gut has been weeks, months, or years in the making.

You don’t just catch leaky gut?

It’s not a seasonal thing?

A leaky gut could be caused by diet, medications, and or other lifestyle factors.

I know from my own research that NSAID usage causes damage to this intestinal barrier. Foods, alcohol, personal hygiene products are other parts of those lifestyle factors. We’ll detail out those foods, alcohol, and personal hygiene products in later posts and pages here at the Natural Cure for Eczema web site.

When those tight junctions we just covered, aren’t so tight, then undigested food particles, toxins, microbiome, and other intestinal contents leak past that barrier into the body and bloodstream.

What causes that intestinal hyperpermeability? What causes a leaky gut?

Zonulin. It’s the protein that regulates the permeability of tight junctions between epithelial cells. Too many zonulin proteins equal too many open doors through the intestinal barrier.

Zonulin is an inflammatory protein first discovered by Alessio Fasano and his research team in 2000.

Doctor Fasano research showed that that the two most powerful zonulin triggers are gluten and gut bacteria.

I’m fairly certain that our bodies wouldn’t produce substances that do not make for optimal health.

Why would zonulin open the intestinal floodgates? Why would there be a mechanism that allowed intestinal contents to escape the intestinal tract?

Is this a case of zonulin gone bad?

Maybe it’s too much of a good thing?

Again, what causes a leaky gut?

Is There a Good Side to Zonulin?

Is there a good side to zonulin?

Buried deep down in many of those page after page of Google search results, I found a blog post that, in part, helps to answer this question. Why would our bodies make something that at first glance, would be bad for us? Is there a good side to zonulin?

In an NPR blog post titled, A Protein In The Gut May Explain Why Some Can’t Stomach Gluten

[Zonulin] helps regulate leakiness in the gut by opening and closing the spaces or “junctions” between cells in the lining of the digestive tract. Zonulin is triggered by harmful bacteria, and offers important protection to the body: If you accidentally eat a food contaminated with salmonella, you rely on zonulin to help trigger diarrhea and flush out the bugs.

[ … omitted text … ]

… the discovery of zonulin is part of a larger, evolving picture. “This molecule is extremely important in a lot of illness, from Type 1 diabetes to other autoimmune diseases. Many illnesses link back to loss of barrier function in the gut.” Soon, a trial will begin to test whether it’s possible to shut down zonulin production in the gut for a few hours.

Take a few minutes to read though the NPR blog post.

We know from our own literature research that the protein zonulin helps regulate leakiness in the gut by opening and closing the spaces or junctions between cells in the lining of the intestinal tract.

In the Fasano literature on PubMed titled: Zonulin, regulation of tight junctions, and autoimmune diseases, in part:

This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms so contributing to the innate immune response of the host against bacterial colonization of the small intestine.

I am sure our Neolithic and more recent ancestors had plenty of cases of the occasional ingested harmful bacteria … bad food … and recovered from it. Otherwise, we wouldn’t be reading this stuff on the internet.

The NPR blog post also provides that:

A zonulin response offers important protection to the body: If you accidentally eat a food contaminated with salmonella, [bad food] you rely on zonulin to help trigger diarrhea and flush out the bugs.

Once the pathogen[s] is[are] gone, zonulin levels drop and the tight junctions close.

Perhaps there are other important zonulin functions? I’m sure zonulin isn’t a one-trick pony.

Time will tell?

Zonulin and Microbiome

Doctor Fasano research showed that that the two most powerful zonulin triggers are gluten and gut bacteria.

A Google search of the keywords zonulin and microbiome returns about 21,700 results as of this writing.

Another Google search of the keywords zonulin and gluten returns about 55,500 search results as of this writing.

Again, following Alessio Fasano and his research, this Innovation Partners blog post titled Functionally Understanding the Microbiome provides, in part:

A key target of interest for Fasano is zonulin, a protein that modulates the tight junctions linking the epithelial cells in the intestines, kidneys and lungs as well as the endothelial cells that form the blood-brain barrier.

It was previously believed that these junctions between cells were fixed and impermeable. However, in 2000, a research team led by Dr. Fasano discovered zonulin and identified its role as a modulator of these junctions between cells.

After this discovery, Fasano and others began to revisit the hypothesis of the ‘so-called’ leaky gut syndrome, or intestinal permeability, as a condition with a role in many diseases.

He explains that there is general agreement that many pathological conditions—infectious diseases, autoimmune disorders, neurodegenerative diseases and cancer—have chronic inflammation as a common denominator.

It is also agreed that there are two key components necessary to develop those diseases—genetic predisposition and exposure to environmental triggers.

With the discovery of zonulin, Fasano and his research team now believe there are three additional elements at play in this process—an impaired epithelial/endothelial barrier, a defective immune response and an unbalanced microbiome.

The impaired epithelial/endothelial barrier, which results from an overexpression of zonulin, loosens the junctions between cells, allowing more molecules to pass through the intestinal lining into the body (and vice versa) and exposing the body to more environmental triggers.

If researchers can find ways to regulate levels of zonulin in the body, it could help in the treatment and prevention of these diseases.

Larazotide acetate, a zonulin inhibitor, is scheduled to soon enter Phase 3 clinical trials, and the Fasano lab has recently developed a transgenic mouse model that overexpresses zonulin, which will further aid in defining the role of zonulin in inflammatory diseases.

Much research has been conducted into zonulin, gluten, and leaky gut. No surprises here. Literature such as this, titled, Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines, come to the same conclusion.

Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules

Zonulin and Diet

I could spend hours reading through this trail of Google search results. But, I have chores to get done, dogs to walk, and a host of other activities.

My own conclusion from this research is that I need to rethink what I eat. I need to feed my microbiome to encourage a healthy and diverse population of these beneficial microorganisms. Will doing this promote tight junctions and low zonulin levels.

This literature titled Nutritional Keys for Intestinal Barrier Modulation, suggests this might be the case.

In their conclusion, they provide:

Composition of dietary intake can have significant impact on the microbiota, and consequently on the epithelial barrier. Considering bacteria fermentation, diets enriched in milk fat can promote the increase in barrier permeability and bacterial translocation along with the decrease in TJ proteins and TER. On the contrary, diets, including probiotic bacterial species or prebiotic fibers, strengthen the epithelial barrier by increasing TJ proteins and TER and decreasing permeability and bacterial translocation, thus, preventing or ameliorating the inflammatory state. It remains to be determined by the link between nutrition and microbiota composition. This is a challenging task as the influence of factors, such as genetics, hygiene, and living conditions, are not taken into account in studies comparing distinct populations.

The Zonulin Diet

As I wrap this up to get some much-needed shuteye, a zonulin elimination diet comes to mind. In my own quest to eliminate my eczema, I have greatly increased my intake of fermented foods, in part, based on all of this late night research. I do believe that this has been a significant part.

A Google keyword search of zonulin and fermented foods comes back with about 31,100 results.

Among them, is this National Healthline blog post titled The Leaky Gut Diet Plan: What to Eat, What to Avoid, seems to hit the mark on and align to the research.

Take a look, it’s and informative read. The post closes with this sentence:

You can also take probiotic supplements, reduce stress, limit NSAID use, avoid alcohol and get more sleep.

So, there is one thing that I have come away with, in all this late-night research, it’s that there is no one thing that is the eczema cure all.

No magic pills.

It’s a lifestyle issue that got me here, so it’ll be another lifestyle change to fix it.

We’ll talk more on our zonulin diet, or rather our zonulin elimination diet in future posts.

What is a Leaky Gut: References:

Nutritional Protocol for the Treatment of Intestinal Permeability Defects and Related Conditions
https://www.naturalmedicinejournal.com/journal/2010-03/nutritional-protocol-treatment-intestinal-permeability-defects-and-related

What is Leaky Gut — And What Can You Do About It?
https://blumhealthmd.com/2018/01/27/what-is-leaky-gut-and-what-can-you-do-about-it/

Leaky Gut As a Danger Signal for Autoimmune Diseases
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

Zonulin, regulation of tight junctions, and autoimmune diseases
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384703/

Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer
https://www.ncbi.nlm.nih.gov/pubmed/21248165

Zonulin: A Discovery That Changed the Way We View Inflammation, Autoimmune Disease and Cancer
https://www.jillcarnahan.com/2013/07/14/zonulin-leaky-gut/

A Protein In The Gut May Explain Why Some Can’t Stomach Gluten
https://www.npr.org/sections/thesalt/2015/12/09/459061317/a-protein-in-the-gut-may-explain-why-some-cant-stomach-gluten

Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin
https://www.ncbi.nlm.nih.gov/pubmed/11193578

The Leaky Gut Diet Plan: What to Eat, What to Avoid
https://www.healthline.com/nutrition/leaky-gut-diet

Inclusion of Fermented Foods in Food Guides around the World
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303846/

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