Causes of Gluten Sensitivity
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Underlying conditions
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| The normal intestine |
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Wheat proteins interact with the immune system by means of DQ2-mediated programmed cell death (apoptosis) of the gut in sensitive individuals. New research is finding that the celiac gut may be predisposed to sensitivity in the absence of HLA genetic factors.
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| How diet proteins reach the blood |
In the normal gut, proteins are digested to peptides by pepsin (stomach), trypsin and chymotrypsin (derived from the pancreas and activated in the gut). Peptides are further digested when they enter the villi, where brush border peptidase break proteins into amino acids. Over much of the small intestine only small solutes, like water, can cross the tight junctions, however some regions of the intestine peptides as large as 500 daltons (4 amino-acids residues in length can cross).
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| The gluten sensitive gut |
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There is a growing body of evidence that the gluten-sensitive intestine differs from the normal gut. Several gluten peptides can infiltrate the region behind the cells lining the small intestine. The "33mer" of α-2 gliadin is a magnitude larger than the maximum size allowable by the barrier around the cell, the tight junctions. Omega-5 gliadin peptides have been found in the blood stream of people with exercise-induced anaphylaxis, aided by salicylates. And the innate "25mer" is capable of reaching mononuclear cells in celiac gut, but in normal gut is broken down by brush border peptidases. It may be a lower peptidase activity that explains the presence of these peptides behind the brush border membrane. Recently, it was found that an α-9 gliadin peptide was capable of binding the "CXCR3" receptor, increasing zonulin production and weakening tight junctions, this may explain how, generally, larger peptides can enter the gluten-sensitive gut.
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