Leaky gut syndrome refers to the weakened gut barrier that readily exposes individuals to food antigens, toxins, and foreign microbes. A major task of the intestinal mucosa is to prevent harmful substances from penetrating the mucosa and into the internal environment of the body. When this protective function is disrupted, creating “leaky gut, it increases inflammation and triggers or exacerbates autoimmune disorders.

What Causes “Leaky Gut”? 

The causes of intestinal permeability are bacterial overgrowth, food sensitivities, NSAIDs, antibiotics, autoimmunity, infections, stress, and alcohol consumption.

What Are the Factors that Determine “Leaky Gut”?

Our office provides a simple blood test that shows imbalances in zonulin, histamine, diamine oxidase (DAO), and lipopolysaccharides (LPS).


Zonulin is a protein that leads to the breakdown of tight gap junctions in the GI lining, tearing down the body’s defenses and opening up the system to increase inflammation.

  • HIGH zonulin: may associate with bacteria, yeast, celiac disease, autoimmune disorders, insulin dependent diabetes, multiple sclerosis & rheumatoid arthritis
    • Progressively elevated zonulin levels may also be an early marker of diabetes, autoimmune conditions, and allergies.
  • LOW zonulin: not clinically significant


Histamine is a chemical that plays an important role not only in anaphylactic allergy, but also at diseased sites within the gastrointestinal tract.

  • HIGH histamine: Besides allergens caused by mast cell degranulation, high levels of histamine can also be due to gut permeability by activating T cells in our body and food that contains high histamine.
  • Some high histamine foods:
    • Very High: Aged or fermented foods: kimchi, sauerkraut, yogurt or kefir, kombucha, aged cheese, alcohol of any kind, vinegar, and cured meat. Fish and seafood, especially canned or smoked fish.
    • Medium: Spinach, eggplant, mushrooms, tomatoes, canned vegetables, dried fruit, avocados, strawberries, papaya, pineapple, and leftovers.
  • LOW histamine: associates with fatigue, depression, & certain type of schizophrenia


DAO is one of the major enzymes involving in degrading extracellular histamine.

  • HIGH DAO: compensatory response for higher levels of histamine from dysbiosis, immune dysregulation of foods
  • Low DAO: correlates with poor mucosal integrity, indicate poor gut function, and cause high levels of histamine. Low DAO activity in serum or plasma has been reported in patients with urticaria, Crohn’s, or celiac disease.
    • Many medications, and alcohol and its degradation product, acetaldehyde, are known to inhibit DAO.


LPS is a major constant of gram-negative bacteria cell membrane, as well as a bacterial endotoxin made by bacteria in the body. LPS elicits strong immune responses in our body.

  • HIGH LPS: associates with bacterial infections, food sensitivities, chronic inflammation, autoimmunity, digestive disorders, and neurological conditions.
  • LOW immune reaction to LPS IgG/IgA/IgM indicates immune dysfunction.


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Author Anna Chung Patient Care Coordinator

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