Gluten Sensitivity is an umbrella term that refers to any and all problematic health responses to gluten in any body system. We first defined gluten sensitivity in our ground breaking text, Recognizing Celiac Disease first published in 2006. Gluten Sensitivity includes celiac disease, gluten allergy, and non-celiac gluten sensitivity reactions.1
Under Pathophysiology in Recognizing Celiac Disease, we confidently published the fact, against the opinion of some noted specialists but in accord with others, that “non-celiac gluten sensitivity” exists as a condition distinct from celiac disease and which must be distinguished from celiac disease for proper treatment of both.
Today, although there lacks a general agreement for the term “gluten sensitivity,” the medical community has accepted the reality of non-celiac gluten sensitivity.
As a result, researchers are calling this condition the “new frontier.” As Dr. Lundin has stated, “We are still challenged with finding stricter clinical criteria for the condition, developing a usable clinical approach for gluten challenge in these individuals, and understanding the pathogenesis of the condition.”2
- Celiac disease is characterized by a specific immune reaction in the small intestinal lining that is both an innate response (inflammatory) and a humoral response (antibody production) to peptides of gluten that leads to malabsorption of nutrients and increased intestinal permeability (leaky gut).3 The humoral antibody response involves the production of immunoglobulin A (IgA) and immunoglobulin G (IgG). Only persons who have inherited this immune response are at risk to develop celiac disease. Celiac disease results in malabsorption and any of a great number of health problems that can develop from the toxic action of gluten peptides entering the body through a leaky gut.
- Gluten allergies are immunoglobulin E (IgE) mediated immune responses where hives, asthma, and similar reactions develop. Allergy involves the production of specific antibodies to specific antigens, which would be a peptide of gluten. For example, wheat allergy commonly targets gliadin as the antigen. IgE immune responses appear to be inherited.
- Non-celiac gluten sensitivity can be diagnosed in those patients with gluten intolerance who do not develop antibodies that are typical either of celiac disease or of wheat allergy and who do not suffer from lesions in the duodenal mucosa characteristic of celiac disease.4 Symptoms that occur soon after gluten ingestion rapidly improve after gluten withdrawal and relapse in a few hours or days after gluten challenge.5
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Non-celiac gluten sensitivity is an innate immune response producing mild inflammation (Marsh I class) of the small intestine lining to gluten when present in the diet but negative to production of the anti-EMA, and anti-tTG immunoglobulins (humoral response), which are autoantibodies mounted in celiac disease.
The mildly inflamed mucosa which is observed much more frequently in non-celiac gluten sensitivity than celiac disease itself have been recently referred to as lymphocytic enteropathy.6 Importantly, the density of IELs (intraepithelial lymphocytes) in intestinal mucosa samples was higher in non-celiac gluten sensitivity patients compared with disease controls, independent of gluten challenge, although lower than the level for treated celiac disease patients.3
Half of patients have anti-AGA antibodies, which are antibodies against gliadin itself. Half of the non-celiac gluten sensitivity patients have the genes encoding DQ2 or DQ8 molecules in their HLA system.6 This disorder is still being clarified.
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- A non-celiac gluten-sensitivity commonly occurs in allergic patients. Based on the high prevalence of non-celiac gluten sensitivity in allergy, it is recommended that biopsy should be part of the routine investigation of allergic disease to offer the benefits of treatment with a gluten free diet to the patients.7
- More research is needed to help disentangle celiac disease from non-celiac disease gluten sensitivity and to understand the mechanisms of gluten-associated neurologic and psychiatric complications. These central nervous system effects are not trivial. Therefore, given the under-diagnosis and potential health consequences, this suggests the value of developing better ways of detecting and preventing the potential complications of these disorders.8
Who Is At Risk For Non-Celiac Gluten Sensitivity?
This needs to be clarified, however, many people appear to experience non-celiac gluten sensitivity as an inflammatory response to gluten in the diet.
What Health Problems Can Develop?
Both intestinal and non-intestinal symptoms are involved.
- Gastrointestinal.
- Bloating.
- Abdominal pain.
- Abdominal distention.
- Nausea.
- Diarrhea.
- Constipation.
- Diarrhea alternating with constipation.
- Gastrointestinal reflux disease.
- Non-Gastrotintestinal.
- Erythema (redness of skin).
- Eczema.
- Allergies.
- Headache.
- Muscle contractions.
- 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.”
- Inattention. Children may not pay attention, whine or cry often.
- Harmful Effect on the Mind.
- 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.
What Should I Do If I Think I Have Gluten Sensitivity?
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 both disorders. In either celiac disease or non-celiac gluten sensitivity, blood tests for anti-gliadin antibodies (AGA) can be done that specifically test for antibodies targeting gluten in the body. Other tests that determine increased intestinal permeability (leaky gut) include Breath Hydrogen Test and Sugar Absorption Test. Both of these tests are simple and non-invasive.
- Libonati, Cleo. Recognizing Celiac Disease, p. IX [↩]
- Lundin KE. Non-celiac gluten sensitivity – why worry? BMC Med. 2014 May 23;12:86. doi: 10.1186/1741-7015-12-86. [↩]
- Brottveit M, Beitnes AC, Tollefsen S, Bratlie JE, Jahnsen FL, Johansen FE, Sollid LM, Lundin KE. Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity. Am J Gastroenterol. 2013 May;108(5):842-50. doi: 10.1038/ajg.2013.91. [↩] [↩]
- Czaja-Bulsa G. Non coeliac gluten sensitivity – A new disease with gluten intolerance. Clin Nutr. 2014 Aug 29. pii: S0261-5614(14)00218-0. doi: 10.1016/j.clnu.2014.08.012. [↩]
- Caio G, Volta U, Tovoli F, De Giorgio R. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterol. 2014 Feb 13;14:26. doi: 10.1186/1471-230X-14-26. [↩]
- Czaja-Bulsa G. Non coeliac gluten sensitivity – A new disease with gluten intolerance. Clin Nutr. 2014 Aug 29. pii: S0261-5614(14)00218-0. doi: 10.1016/j.clnu.2014.08.012. [↩] [↩]
- Massari S, Liso M, De Santis L, Mazzei F, Carlone A, Mauro S, Musca F, Bozzetti MP, Minelli M. Occurrence of nonceliac gluten sensitivity in patients with allergic disease. Int Arch Allergy Immunol. 2011;155(4):389-94. doi: 10.1159/000321196. [↩]
- Jessica R. Jackson, William W. Eaton, Nicola G. Cascella, Alessio Fasano, and Deanna L. Kelly Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity. Psychiatr Q. Mar 2012; 83(1): 91–102. doi: 10.1007/s11126-011-9186-y [↩]