The Overlap of Irritable Bowel Syndrome and Noncoeliac Gluten Sensitivity

Anupam Rej; David S. Sanders


Curr Opin Gastroenterol. 2019;35(3):199-205. 

In This Article

Wheat Components Other Than Gluten

The wheat grain has been demonstrated by proteomic analysis to contain several individual components. Wheat grains constitute about 10–12% of protein, of which 80% is gluten.[26] Whilst there has been a focus on gluten leading to the induction of symptoms in NCGS and IBS, several other components of wheat have been implicated as a causal factor, including amylase/trypsin inhibitors (ATIs), wheat germ agglutinins (WGAs) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs).[6]

Wheat ATIs represent a family of up to 17 proteins[27] and represent around 4% of the total wheat proteins.[28] ATIs are associated with baker's asthma,[29] and have been suggested as an aetiological mechanism in NCGS by activation of the innate immune system. Wheat ATIs have been demonstrated to drive intestinal inflammation via the activation of toll-like receptor 4, in vitro and in vivo.[30] The activation of toll-like receptor 4 is thought to lead to the upregulation of maturation markers and release of pro-inflammatory cytokines, leading to an innate immune response.[27] It is also thought that modern hexaploid wheat contains higher ATI activity than older variants.[27]

Lectins are generally regarded as antinutrients within food, with WGA being the best studied serial grain lectin. WGAs have been demonstrated to induce an inflammatory response by immune cells.[31] They have been demonstrated to affect enterocyte permeability, which could lead to the translocation of microbial and dietary antigens interacting with the cells of the immune system.[31] It is important to note, however, that human data demonstrating the effect of WGA on inflammatory markers is lacking.[31]

Fructans, which are part of the FODMAP family, are the major short-chain carbohydrates present in wheat-based grains. FODMAPs may lead to the initiation of symptoms in patients with NCGS and IBS. They are short-chain carbohydrates, which are poorly absorbed, leading to an increase in small bowel water content and intestinal transit.[32] They are subsequently fermented in the large bowel, leading to intestinal gas production and distension, which may lead to symptom generation in individuals.[33] Interestingly, similar physiological responses have been noted in healthy individuals as well as those with IBS. It is likely that colonic hypersensitivity to distension in individuals with NCGS and IBS is likely to be the pathophysiological mechanism.[34] FODMAPs are generally considered to be beneficial with regards to epithelial cell integrity and health.[6]

As can be seen from above, there are several components other than gluten, which have been implicated in the pathophysiology of NCGS and IBS. As a result of this, the terminology of noncoeliac wheat sensitivity (NCWS) and noncoeliac wheat protein sensitivity (NCWPS)[35] have also been used to describe the clinical entity of NCGS.