The Overlap of Irritable Bowel Syndrome and Noncoeliac Gluten Sensitivity

Anupam Rej; David S. Sanders

Disclosures

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

In This Article

Pathophysiology

Whilst the pathophysiology of NCGS is not fully understood, it has been hypothesized that individuals with NCGS may have non-IgE-mediated wheat allergy.[18] In a large study by Carroccio et al.,[16] it was noted that the majority of individuals with wheat sensitivity were demonstrated to be suffering from cow's milk protein sensitivity. This condition is well known in the paediatric population, and could potentially suggest a non-IgE-mediated food hypersensitivity.[18] Also, a higher frequency of food allergy in the paediatric age was noted in the study, which would support this hypothesis.[18]

There have been conflicting studies on the effect of NCGS on intestinal permeability. Ex-vivo human duodenal biopsies have demonstrated an increase in intestinal permeability in individuals with NCGS.[19] Elevated levels of fatty acid-binding 2 protein, a marker of intestinal epithelial cell damage, have been demonstrated to be elevated in patients with NCGS, also supporting the hypothesis of compromised intestinal epithelial barrier integrity.[20] However, the converse of this has also been demonstrated. In-vivo testing using lactose/mannitol testing demonstrated significantly reduced intestinal permeability in individuals with NCGS in comparison with controls (P = 0.03).[21] Further research is required before any definitive conclusions can be made on the effect of NCGS on intestinal permeability.

Like NCGS, the pathophysiology of IBS is unclear, although pathophysiological abnormalities including visceral hyperalgesia, altered gut motility, genetic and psychological factors have been proposed.[22] It is known that individuals with IBS may have sensitivity to gluten, although the mechanism leading to symptoms is unclear. Gluten has been demonstrated to effect bowel barrier function in patients with IBS. A randomized controlled trial (RCT)[23] in 45 patients with IBS-D involved a 4-week trial of either a gluten-free diet (GFD) or gluten-containing diet (GCD). Small bowel permeability was demonstrated to be higher on a GCD, which was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients. Expression of tight junction proteins (ZO-1, occludin and claudin-1) were demonstrated to be lower on a GCD. Another study[24] also demonstrated changes in tight junction proteins following gluten in IBS. This study demonstrated alterations in myosin light chain phosphorylation and claudin-15 and claudin-2 expression with gluten. These findings could potentially explain the changes in intestinal permeability seen in patients with IBS following gluten challenge.[24]

Interestingly, in 36 patients with IBS and suspected food intolerance, confocal laser endomicroscopy (CLE) has shown immediate and dramatic mucosal responses to several antigens. Mucosal responses to antigens were seen in 22 of the 36 patients, including wheat (n = 13). Intraepithelial lymphocytes increased, epithelial leaks/gaps formed and intervillous spaces widened in individuals who had mucosal responses to antigens.[25] This interesting method may help to identify individuals with IBS who have food sensitivity.

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