Research Critique: Gluten Free Diet Normalizes NCGS and CD Intestinal Permeability?

By Dante Moroni

Note: This article is non-peer reviewed and self published. Any statement within are for entertainment purposes and curiosity sake. In no way should any piece from this article be taken as medical advice. This article is also a work in progress and will be updated as necessary by the author.

It is hypothesized that Increased Gut Permeability may be one of the first steps in developing gastrointestinal autoimmune diseases like Celiac Disease, Type 1 Diabetes, and Inflammatory Bowel Disease.1 What predisposes one to develop the disease depends on a variety of environmental and genetic factors and is still being investigated. A 2011 study by Sapone et al. quantified in vivo intestinal permeability in patients with active Celiac Disease (CD), patients already diagnosed with NCGS, and healthy controls.2 Their results agreed with previous ex vivo results of biopsied cells exposed to gliadin, in that the CD cells had significantly greater permeability than normal cell lines.3

Example of tight junction between enterocytes. Source.

I feel compelled to review this 2011 study as it is one that is in dire need of a follow up. The authors concluded that NCGS patients have significantly lower permeability, measured by the lactulose/mannitol test, than CD patients, AND healthy controls. To the untrained eye this may look like another blow to the evidence supporting NCGS as a clinical entity. However, what the authors fail to explain, and which I have only the option of assuming, is that the NCGS patients were on a gluten free diet at the time of testing. The controls were likely consuming gluten as part of a standard diet. Considering this critical information, my alternative interpretation of the data is as follows.

Intestinal Permeability is normalized, or even healthier in Non-Celiac Gluten Sensitivity following a gluten free diet than controls. I am not surprised by this as zonulin driven intestinal permeability has been shown to increase in ALL enterocyte tight junctions exposed to Gliadin regardless of genetics.3 Those healthy controls may have had higher permeability than NCGS due to their consumption of gluten. This has implications in that a gluten free diet may be beneficial to an even wider population than currently understood.

In order to confirm these results we need a follow up study. The concept would be simple. Again, test intestinal permeability in NCGS patients, but this time have two groups. One would be NCGS patients on a gluten challenge of 10g/day. The other would be NCGS patients on a gluten free diet (GFD). You would not need to blind the study as the LA/MA result is mostly an involuntary outcome (e.g. It cannot be influenced by knowing whether or not you are consuming gluten). You would also have two groups of healthy controls, one on gluten, and one on a GFD. Comparing the four groups would let us differentiate genetic mucosal divergences between NCGS and healthy controls.


  1. Alessio Fasano, Donohue AS. Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nature Reviews Gastroenterology & Hepatology. 2005;9:416-422.
  2. Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo I, Esposito P, Ferraraccio F, Cartenì M, Riegler G, De Magistris L, Fasano A. BMC Medicine. Divergence of Gut Permeability and Mucosal Immune Gene Expression in Two Gluten Associated Conditions: Celiac Disease and Gluten Sensitivity. 2011;9:9-23
  3. Drago S, El Asmar R, Di Pierro M, Clemente M, Tripathi A, Sapone A, Thakar M, Iacono G, Carroccio A, D’Agate C, Not T, Zampini L, Catassi C, Fasano A. Gliadin, Zonulin and Gut Permeability: Effects on Celiac and Non-Celiac Intestinal Mucosa and Intestinal Cell Lines. Scandinavian Journal of Gastroenterology. 2006;4:408-419.
  4. Duerksen D, Wilhelm-Boyles C, Parry D. Intestinal Permeability in Long-Term Follow-up of Patients with Celiac Disease on a Gluten-Free Diet. Digestive Diseases and Sciences. 2005;50:785-790.