Gliadin peptides initiate intestinal permeability through the release of zonulin, thereby enabling paracellular translocation of gliadin and other dietary and microbial antigens, which by interacting with the immune system give rise to inflammation. In this manner, a vicious cycle is created in which, as a consequence of the persistent presence of pro-inflammatory mediators, intestinal permeability will increase even further. High zonulin levels (together with increased intestinal permeability) have been observed in autoimmune and inflammatory diseases like CD, multiple sclerosis, asthma and inflammatory bowel disease and the haptoglobin polymorphism is associated with rheumatoid arthritis, ankylosing spondylitis, schizophrenia and certain types of cancer [32]. The substitution of whole grain (mainly based on milled wheat) for refined grains products in the daily diet of healthy moderately overweight adults for six weeks did not affect insulin sensitivity or markers of lipid peroxidation and inflammation [66]. Consistent with these finding are the results of Brownlee et al. [67], who showed that infrequent whole-grain consumers, when increasing whole grain consumption (including whole wheat products), responded with no improvements of the studied biomarkers of cardiovascular health, including insulin sensitivity, plasma lipid profile and markers of inflammation. The substitution of refined cereal grains and white bread with three portions of whole wheat food or one portion of whole wheat food combined with two servings of oats significantly decreased the systolic blood pressure and pulse pressure in middle-aged, healthy, overweight men and women, yet none of the interventions significantly affected systemic markers of inflammation [70]. Biesiekierski et al. [12] undertook a double-blind randomized, placebo-controlled rechallenge trial to investigate the influence of gluten in individuals with irritable bowel syndrome but without clinical features of CD, who reached satisfactory levels of symptom control with a gluten-free diet. After screening the participants, about 50% of the individuals in both the gluten and placebo group were HLA-DQ2 and/or HLA-DQ8 positive. Participants received either gluten or placebo together with a gluten-free diet for six weeks. Endpoints in the study were symptom assessments and biomarkers of inflammation and intestinal permeability. The patients receiving gluten reported significantly more symptoms compared to the placebo group. The most striking outcome of this study was that for all the endpoints measured, there were no differences in individuals with or without HLA-DQ2/DQ8, indicating that the intake of gluten can cause symptoms also in individuals without this specific HLA-profile
Nutrients 2013, 5(3), 771-787; doi:10.3390/nu5030771
Review
The Dietary Intake of Wheat and other Cereal Grains and Their Role in Inflammation
Karin de Punder 1 and Leo Pruimboom