stop me if this has been posted here before.

PubMed 2006 study on gliadin/zonulin interactions.

Abstract conclusion: "Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules."

Translation: Doesn't matter whether you are celiac or not, gliadin (present in all grains to some degree) is demonstrated to increase gut permeability.

I work in pharma (no don't hit me, I'm merely a paper pusher; think of me as insider insight). The way one of my scientist colleagues explained this to me is: "think of gliadins as a zipper protein that 'unravels' gut cells at a molecular level. The stronger the gliadin, the more efficient the 'zipper'. Modern wheat / high gluten varieties contain the strongest forms we currently know of". (n.b. Colleague is also Primal/Paleo after dealing with multiple food sensitivities).

Once the gut becomes permeable to foreign macromolecules (proteins), continued chronic exposure to these proteins (as well as the various gut flora) in the bloodstream generally leads to a choose-your-own-adventure of autoimmune spectrum issues as the body succumbs to chronic overstimulation of the inflammatory response.

The catch, of course, is that you're talking about the human body, which is a highly complex system and one that cannot be adequately modelled by rats, flatworms, molecules in Petri dishes or otherwise. How one person's immune system reacts has no indication of how yours will, and there's a whole spectrum of variables there as well (what shape is your cortisol signalling system in? how much stress are you habitually exposed to? What is your overall health / fitness level? What is your diet like? How clean is your environment/what pollutants are you regularly exposed to? Is your gut flora healthy, or has it been compromised/unbalanced by antibiotics?...) Etcetera, etcetera, etcetera.

is it any wonder that modern medicine so tightly focusses on symptoms at the cost of systemic / holistic solutions? Symptoms are simple. $clinical trial drug: does it improve pt outcome (yes/no). $adverse effects? (yes/no) - and so on. Plus there's a whole lot of money to be made in the pharma industry, where diet/lifestyle... that's a riskier, squishier pursuit.

The most frustrating part to me is where scientists and the medical industry often dismiss dietary science as "statistically flawed" because, well, you can't double-blind a diet study easily. I always feel like asking what the statistical incidence of placebo effect actually is - you'd think they'd be able to trend for it.