Examine publishes rigorous, unbiased analysis of the latest and most important nutrition and supplementation studies each month, available to all Examine Members. Click here to learn more or log in.

In this article

A hole in the bucket: gliadin and intestinal permeability

Understanding what happens at the intestinal barrier is key for understanding reactions to wheat.

Study under review: Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with NonCeliac Gluten Sensitivity

Introduction

As you learned in last month’s Study Deep Dives, celiac disease, wheat allergy, and non-celiac gluten sensitivity (NCGS) are distinct clinical diagnoses that share a common treatment: avoiding gluten. Confusing matters is the fact that NCGS is a diagnosis of exclusion, meaning something that's left after other possible causes have been excluded. To diagnose NCGS, wheat allergy and celiac disease (CD) must be ruled out and the person being tested must show a positive response to a gluten-free diet. Ideally, the dietary challenge would be performed in a blinded manner, as many people who believe they need a gluten-free diet may actually be suffering from a nocebo effect (when the expectation of potential problems triggers a negative effect) when undergoing a challenge. Due to these difficulties, finding pathophysiological differences between CD and NCGS has become the topic of increasing amounts of research.

Individuals with NCGS suffer adverse reactions to gluten-containing foods, though this response does not involve a T-cell (adaptive immune) mediated process. The immune system is typically divided into two categories, innate immunity offers non-specific protection like the physical barrier of the skin or immune cells that attack foreign invaders, while adaptive immunity is a response to a specific antigen which is ‘remembered’ by the body. It has been suggested[1] that the commonality between celiac disease and NCGS may actually be a shared problem of intestinal barrier function. In a healthy gut, the internal lining should be impermeable to large molecules such as gliadin (a component of gluten) due to properly functioning tight junctions, which seal off the gap between cells. However, for the past 15 years it has been known[2] that, at least in people with celiac disease, intestinal exposure to gluten, specifically gliadin, leads to an increase in intestinal permeability, which is mediated by increased release of a protein known as zonulin. Interestingly, increased intestinal permeability seems to be independent of celiac disease pathology, as many first-degree relatives of celiac patients[3] have increased permeability without having celiac disease. The genetic component of celiac disease is highlighted in Figure 1.

Figure 1: The genetic component of celiac disease

Cytokines[4] are proteins secreted by cells, and are one of the primary methods of cell-to-cell communication. They can be both pro-inflammatory and anti-inflammatory, and can have autocrine function (act on the cells that secrete them), paracrine function (act on nearby cells), or endocrine function (act on distant cells). In the ongoing effort to classify NCGS, cytokine secretions could potentially provide biomarkers for detecting differences among NCGS, CD, and wheat allergy.

The objectives of this study were to evaluate intestinal barrier function and cytokine secretion from intestinal biopsies of patients with CD (both active and in remission) as well as NCGS and non-celiac controls, after being exposed to partially-digested pepsin-trypsin treated gliadin (PT-gliadin, which is cytotoxic in celiac disease)[5]).

The intestinal lining of people with and sometimes without the symptoms of celiac disease can get leaky when exposed to gliadin, a component of gluten. Cytokines may play a role in this process. The goal of this study was to examine how intestinal tissue removed from the bodies of participants with celiac disease (active and in remission), participants with non-celiac gluten sensitivity (NCGS), and healthy controls respond to partially-digested gliadin.

Who and what was studied?

Become an Examine Member to read the full article.

Becoming an Examine Member will keep you on the cutting edge of health research with access to in-depth analyses such as this article.

You also unlock a big picture view of 400+ supplements and 600+ health topics, as well as actionable study summaries delivered to you every month across 25 health categories.

Stop wasting time and energy — we make it easy for you to stay on top of nutrition research.

Try free for two weeks

Already a member? Please login to read this article.

What were the findings?

Become an Examine Member to unlock this article.

Already a member? Please login to read this article.

What does the study really tell us?

Become an Examine Member to unlock this article.

Already a member? Please login to read this article.

The big picture

Become an Examine Member to unlock this article.

Already a member? Please login to read this article.

Frequently Asked Questions

Become an Examine Member to unlock this article.

Already a member? Please login to read this article.

What I should know?

Become an Examine Member to unlock this article.

Free 2-week trial »

Already a member? Please login to read this article.

Other Articles in Issue #08 (June 2015)