Nevertheless, this study is a goldmine of valuable ideas that no one is touching.
Not all of the study's results should be considered ex vivo. They took intestinal tissue from celiacs in remission and from non-celiac controls with digestive complaints, and measured the amount of zonulin in those tissues before performing any experiments on them.
Remarkably, they found that celiacs produce 30 times as much zonulin as non-celiacs, even though the non-celiacs were not eating gluten-free diets while the celiacs had been off gluten for over two years!
Here's a graph of their data:
This is remarkable because even though the point of the study was to show that gluten increases zonulin production, the controls were eating gluten yet had infinitesimal levels of zonulin production, while the celiacs had not eaten gluten for at least two years yet still had very high levels of zonulin production. This suggests that something besides gluten may be causing zonulin production in celiacs.
They found similar, though less dramatic, results for intestinal permeability:
Here they measured trans-epithelial electrical resistance (TEER) of intestinal tissue taken from gluten-free celiacs and gluten-eating controls. TEER is an estimation of the leakiness of the gut, where a lower value indicates a greater level of leakiness or permeability. They found that tissues taken from controls who had been eating gluten had three-fold less leakiness compared to celiacs who had been off gluten for over two years. This, again, suggests that something besides gluten may be contributing to leaky gut in people with celiac.
What is causing the persistently elevated zonulin in celiacs, or the somewhat less severe persistent elevation in gut permeability? It could just be that these subjects need to adhere to a gluten-free diet more strictly or for much longer than two years to fully resolve these issues. Or, it may be that certain types of intestinal dysbiosis (improper balance of bacteria and yeasts in the intestines) prime genetically susceptible individuals to develop celiac in response to gluten.
Dr. Fasano's group has also published a study showing that bacteria such as E. coli and Salmonella stimulate zonulin production in isolated intestinal tissue, and another recent study showed that short-term inoculation of rats with E. coli and Shigella enhanced the ability of gluten to cause intestinal damage while inoculation with Bifidus bacteria virtually eliminated gluten's ability to cause damage. Neither of these studies show that dysbiosis contributes to celiac, or that it is responsible for the persistence of zonulin production on a gluten-free diet, but they offer strong support to the plausibility of these hypotheses.
In any case, it is true that Dr. Fasano's 2006 study showed that gluten was capable of increasing zonulin and consequently increasing gut permeability ex vivo in intestinal tissue from both celiac and non-celiac subjects. Still, the effect in tissue taken from non-celiac individuals is pretty small.
Here's the effect on zonulin:
Similar results were also seen for TEER, their estimation of gut integrity:
Here again we see that although gluten decreased gut integrity even in tissue isolated from subjects without celiac who were eating gluten as part of their normal diet, it never declined even close to the level seen in celiacs who had been gluten-free for two years.
Ultimately, however, the most remarkable finding of this study is the massive persistence of zonulin production and leaky gut in celiacs even after they have been gluten-free for two years. The authors noted this in their conclusion:
Nevertheless, zonulin is markedly up-regulated in subjects affected by [celiac disease], even when treated with a gluten-free diet. This up-regulation is associated with increased baseline gut permeability, and an increased amplitude and duration of gluten-induced zonulin release when compared with non-[celiac disease] intestinal samples. Despite the presence of measurable zonulin response in both [celiac disease] and non-[celiac disease] subjects, [celiac disease] patients appear to reach a critical threshold of intestinal permeability upon gliadin exposure that is not reached in non-[celiac disease] intestinal mucosa.
This is remarkable because it suggests that celiac is about more than just genes and gluten. I will revisit this topic when I get my food toxins and food intolerances series going. In the mean time, I owe you all a sequel to my last LDL post, and then it'll be back to fructose for a while.