Treatment Guide

Gluten Sensitivity (Non-Celiac Gluten Sensitivity)

Gluten Sensitivity is an umbrella term defined as “any and all problematic health responses to gluten in any body system.” (Recognizing Celiac Disease, p. IX)

Anyone can experience Gluten Sensitivity as a normal immune response to the abnormal presence of gluten in blood or body tissues.

Non-Celiac Gluten Sensitivity can develop if gluten, or rather, harmful partially digested fragments of gluten, wrongly pass through the small intestinal lining into our bloodstream.  From the blood, these protein fragments can harm any of our body tissues.

Factors Leading to Gluten Sensitivity Reactions

Two important factors that may subject non-celiac people to a gluten sensitivity reaction are high gluten load, and increased permeability of the small intestinal lining, also called “Leaky Gut Syndrome.”

1.  High Gluten load

A high gluten load simply means we are eating a diet that contains too much gluten. Of course, the more gluten we eat, the greater is the risk of protein fragments entering our bloodstream.

2.  Increased Permeability of the Small Intestinal Lining (Leaky Gut Syndrome)

Gluten may drive the immune system, even outside the gastrointestinal tract (extra-intestinal), to cause other diseases that we don’t call celiac disease, but which are still derived from gluten.1 Studies reveal extra-intestinal manifestations with positive blood tests for anti-gliadin antibodies without evidence of celiac disease.  This finding indicates gluten entering the bloodstream via increased membrane permeability of the small intestine.

Increased Intestinal Permeability (Leakage)

Increased permeability of the small intestinal lining, also called hyperpermeability, refers to alteration of the complex barrier system that separates what’s in our gut from the rest of our body. This protective system determines what substances may be allowed to cross from the inside of our small intestine to our bloodstream. An abnormal barrier allows harmful substances to “permeate” into deeper layers of the intestinal wall and into the bloodstream.

The major defense of the barrier system against permeation by harmful substances is comprised of tight intercellular junctions. Tight junctions (TJ) refer to the regulated spaces between enterocytes (cells forming the surface lining of our small intestine), causing these cells to closely adhere to each other, side-by-side. Disruption of TJ allows harmful substances such as gluten fragments to slip through them.

Only a single layer of epithelial cells separates the contents of our small intestine from the lamina propria (underlying tissues of the small intestine) and the rest of our body. Breaching of this single layer of cells can expose effector immune cells located in the lamina propria to a myriad of microorganisms and food antigens, leading to immune reactions.2

Breakdown of the barrier is implicated in the pathogenesis (development) of acute illnesses such as bacterial translocation leading to sepsis and multiple organ failure. It also has been implicated in several auto-immune disease, including Celiac Disease, Type I Diabetes Mellitus, Autism, Inflammatory Bowel Disease, and atopic disorders such as Asthma, Rhinitis, Eczema, and Allergies.3

Factors Other Than Gluten That Disrupt Tight Intercellular Junctions?

  • Gastrointestinal infections from microbes such as rotavirus, parasites, pathogenic bacteria (Escherichia coli, Clostridium difficile toxins), and mycotoxins (toxins produced by fungi found in stored grain and dried fruit).
  • Fats such as rancid fats, sodium caprate, a medium-chain fat, and sucrose monester fatty acid, a food-grade surfactant, induce significant disruption.
  • Foods such as alcohol, lactose, caffeine, paprika, cayenne pepper, refined carbohydrates, some food preservatives and food additives.
  • Medications such as oral antibiotics, NSAIDS (eg, Aspirin, Advil), corticosteroids, and oral contraceptives.
  • Psychological stress, oxidative stress
  • Intense exercise
  • Aging

Restoring Tight Intercellular Junctions

Correction of the factors that cause Tight Junction disruption and eating a gluten-free diet with foods that have been shown to restore Tight Junction function after injury, such as:

  • EPA and gamma linolenic acid (omega-3 fatty acids).
  • Butyrate  (a short-chain fatty acid).
  • Glutamine (an essential amino acid).
  • Black pepper and nutmeg.

Health Problems That Can Develop?

Mild problems that may come and go include irritability, sluggishness, tiredness, achiness, the “blues”, fatigue, and disinterest in things that should cause interest. With less mental acuity and drive, a person with these symptoms may feel like a “couch potato.” Others may say things like, “What’s got into you?” or “You never want to do things anymore.” Or “You don’t take care of the house like you used to do.” Children may not pay attention, whine or cry alot.

Gluten can wreak havoc throughout the body if leakiness is severe or prolonged. Gluten can affect the mind causing problems like depression and anxiety. Thinking difficulties may develop such as poor attention, judgment and memory or outright confusion. Behavioral problems may include hyperactivity or inappropriate social interaction. In some people, psychotic symptoms can develop which may be reversed on a gluten-free diet. Read more…Symptom Guide.

Gluten Can Have a Harmful Effect on the Mind

When gluten is broken down in the intestines during digestion, peptides are formed.  Certain peptides, called Gluten Exorphine and Gliadorphin, mimic the effects of morphine on the brain if they abnormally enter the bloodstream.  People who are unable to break down these peptides may experience mental health problems.

The same gut-brain mechanism that allows oral medications used to treat mental problems, such as depression, to enter the brain also allows gluten to enter. Neuoroactive compounds [substances that affect the brain] derived from within the intestine can permeate either diseased or healthy mucosa, cross the blood-brain barrier and cause psychiatric, cognitive and behavioral disturbances.4 Both gluten and beta-casein in milk are neuroactive compounds that cross the intestinal lining into the bloodstream and cause the mental symptoms in susceptible people such as autism and schizophrenia.  When gluten is the cause of schizophrenia, studies show that symptoms disappear in 2 weeks but will reappear in 3 days if gluten is again ingested.

What other problems can develop from gluten in the bloodstream?

Wherever gluten goes, it alarms our immune system to react because it damages any tissue it touches. When our body surrounds and encloses it, we form granulomas. These hard nodules can develop in the liver, joints, and skin. Granulomas are like pearls formed by an oyster. Our body encapsulates gluten to keep it from hurting our tissues much like an oyster does a grain of sand that lodges inside of it.

The longer we eat gluten, the greater is our risk of developing other auto-immune disorders such as, Alopecia Areata (hair loss), Psoriasis (skin disorder), Addison’s Disease (adrenal gland disorder), Grave’s Disease (hyperthyroid disorder) and Auto-immune Hepatitis (liver disorder).

In auto-immune disorders, the development of anti-gliadin antibodies may be attributed to the response to food protein [from gluten] and is often not closely related with Celiac Disease. 1

What should I do if I think I have this problem?

If you suspect you have this problem, see your doctor.  He may want to rule out Celiac Disease because Leaky Gut Syndrome is a part of this disorder.  In either condition, blood tests for anti-gliadin antibodies can be done that specifically test for gluten.  Other tests that determine Increased Intestinal Permeability (Leaky Gut) include Breath Hydrogen Test and Sugar Absorption Test.  Both of these tests are simple. Read more…Diagnosis and Testing


  1. Kamaeva OL, Reznikov IP, Pimenova NS, Dobritsyna LV. Antigliadin antibodies in the absence of celiac disease.
  2. Fahardi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003; 18: 479-497.
  3. Liu Z, Li N, and New J. Tight Junctions, leaky intestines, and pediatric diseases. Acta Pediatrica, 2005;94:386-393.
  4. Wakefield AJ, Puleston JM, Montgomery SM, Anthony A, O’leary JJ, Murch SH. Review article: the concept of entero-colonic encephalopathy, autism and opiod receptor ligands. Blackwell Science Ltd, Aliment Pharmacol Ther. 2002; 16:663-674.

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