Rectal mucosa inflammation in non-celiac wheat sensitivity: comparison with duodenal histology

Background and Aims: In recent years an increasing number of studies on Non-Celiac Gluten/Wheat Sensitivity (NCG/WS) have been published but no markers of this condition have as yet been found. Although the NCG/WS clinical presentation often overlaps with IBS, no previous study evacuate colon or rectal histology in NCG/WS patients. Patients and Methods: We performed a prospective study on 78 patients (66 females, 12 males, mean age 36. 4 years) diagnosed with NCG/WS by double-blind wheat challenge, presenting at two tertiary care centers in Italy from January 2015 through September 2016. Data were also collected from 55 control patients either with celiac disease (CD) or with self-reported NCG/WS who tested negative at the wheat challenge. Duodenal immunohistochemistry studies were performed to evaluate the number of intra-epithelial CD3+ lymphocytes (IEL), lamina propria CD45+ immunocytes, CD3+, CD4+ and CD8+ lymphocytes, mast cells, eosinophils, and presence and size of lymphoid nodules. Identical studies were performed on the rectal mucosa of NCWS patients and of self-reported NCG/WS with a negative wheat challenge. Results: In the duodenum, NCG/WS patients showed a significantly higher number of CD3+ IEL, lamina propria (LP) CD4S+ immunocytes and eosinophils than self-reported NCG/WS with a negative wheat challenge. NCG/WS patients with dyspepsia had a higher number of LP eosinophils than those not reporting upper digestive tract symptoms. In the rectal mucosa, NCG/WS patients showed enlarged lymphoid follicles more frequently than self-reported NCG/WS subjects with a negative wheat challenge, and a higher number of CD3+ intra-epithelial lymphocytes and LP CD45+ and eosinophils than control patients. The CD controls had the highest number of immunocytes (CD3+, CD45-P, eosinophils) of the 3 groups studied, both in the duodenum and in the rectum. Conclusions: Both the duodenal and rectal mucosa are inflammed in NCG/WS patients and eosinophils are increased in these districts. NCG/WS could be considered an inflammatory condition of the entire intestinal tract, mainly involving the rectum, and eosinophil infiltration a key candidate player in the pathogenesis of NCG/WS. The study was supported by the Italian Foundation for Celiac Disease (FC) Grant for Project 013/2014.