Leaky gut, or intestinal permeability, and lab testing

Many people with gluten sensitivity and gastrointestinal inflammation develop intestinal permeability, or “leaky gut.” Leaky gut happens when the lining of the digestive tract becomes over-porous and allows toxins, undigested food, and other pathogens into the bloodstream.

These pathogens trigger an immune cascade that results in systemic inflammation, increasing the risk for food sensitivities, inflammation, pain, and autoimmune disease.

The damage doesn’t stop there. Leaky gut is related to “leaky brain,” in which the blood-brain-barrier, a protective membrane around the brain, becomes over-permeable as well. This allows pathogens to enter the brain, leading to a damaging cascade of inflammation.

On my website is more detailed information on the diet and protocols for addressing leaky gut.

Laboratory analysis of leaky gut syndrome

Leaky gut lies at the foundation of most autoimmune and chronic health conditions. Knowing whether you have it helps determine the proper treatment protocols.

To appreciate the best test for leaky gut you first need to understand the tight junctions of the intestinal wall, and what regulates the opening and closing of these junctions.

The cell wall of the intestine is composed of tight junctions, areas where the membranes of adjacent cells join together to form a barrier to the passage of fluid between cells. This is critical for preventing pathogens and other unwanted materials from entering the bloodstream and causing an inflammatory reaction in the immune system.

Our understanding of leaky gut and its relationship to autoimmune disease is based in large part on the discovery of zonulin. Zonulin is a protein that opens up the tight junctions of the intestinal wall, thus regulating how permeable the gut is.

Researchers first discovered zonulin while studying cholera. When given to animal subjects, zonulin created immediate intestinal permeability. This instigated further research into the leaky gut model.

For people with celiac disease, gluten triggers zonulin to open these junctions, thus promoting leaky gut. Zonulin also opens the junctions in the blood-brain barrier for those with celiac disease. But many researchers believe zonulin release is not specific to the celiac population. Some research shows gluten opens these junctions in all people. Occludin is another messenger protein that regulates intestinal permeability.

Zonulin and occludin antibodies

As the gut becomes inflamed and breaks down during leaky gut, the immune system makes antibodies to zonulin and occludin. One way to evaluate leaky gut is to test for elevated zonulin-occludin antibodies. Because the blood-brain barrier also has zonulin and occludin, positive antibodies could indicate a leaky blood-brain barrier as well.

Actomyosin antibodies

Actomyosin antibodies are another indication of intestinal destruction. Actomyosin is a complex of proteins that makes up muscle fibers and contributes to muscular contractions. Antibodies to actomyosin signal a breakdown of the membrane lining the digestive tract and hence leaky gut.

Actomyosin antibodies indicate gut damage is severe enough to break through the cells, not just open the spaces between cells. This type of damage takes longer to repair.

LPS antibodies

We also look at antibodies to lipopolysaccharides (LPS), the compound in the membranes of harmful bacteria that trigger inflammation. Immune cells in the mucosal lining do not interact with LPS unless the walls are breached due to leaky gut. Upon exposure, the immune system produces antibodies to LPS, another marker we can measure to identify leaky gut.

LPS antibodies also signify gut flora dysbiosis, or the overgrowth of harmful bacteria in the digestive tract. When we see LPS antibodies in the bloodstream we know it is causing inflammation throughout the body and may have breached the blood-brain barrier, causing inflammation in the brain.

Antibodies to zonulin, occludin, actomyosin, and LPS are measurable with a blood test, now understood to be the most accurate way to analyze the immune response to intestinal permeability.

Cyrex Array 2

Cyrex Labs offers this test, called Array 2 – Intestinal Antigenic Permeability Screen. If you do not have access to the lab test, then you can just begin the protocols for intestinal permeability I discuss in my brain book. The only problem with not having the lab test done is you don’t have confirmation that leaky gut is the cause of your symptoms, and you cannot confirm whether you have corrected the problem with a follow-up test.

Cyrex Array 2:

1. Measures intestinal permeability to large molecules which inflame the immune system, and identifies the damaging route through the intestinal barrier.

2. Is recommended for patients who:

• Present multiple symptom complaints (including Chronic Fatigue Syndrome).
• Suffer from abnormal immune cell count and function (including autoimmune diseases).
• Complain of food sensitivity and intolerance.

3. Tests for the following antigens:

• Actomyosin IgA
• Occludin/Zonulin IgG
• Occludin/Zonulin IgA
• Occludin/Zonulin IgM
• Lipopolysaccharides

Cyrex also offers two other barrier permeability screens:

Array 20 – Blood-Brain Barrier Permeability, recommended if you:

• Play contact sports during which repeated head trauma occurs.
• Engage in activity that involves force or shock to the head and/or body.
• Have intestinal permeability with abnormal elevation in LPS and/or Occludin/Zonulin antibodies.
• Exhibit changes in cognitive function.

Array 22 – Irritable Bowel / SIBO Screen, recommended if you:

• Have irritable bowels.
• Exhibit symptoms of malabsorption, including weight loss, anemia or fatty stools.
• Have associated conditions such as fatigue, reflux, skin disorders, obesity or food intolerances.

For references on this article, please see Chapters 8 and 9 in my brain book.