Dear Editor,

We read with great interest the brief report by Zanini et al. [1] published on your journal concerning the need to identify duodenal histological features in suspected non-celiac gluten sensitivity (NCGS) in order to provide new insights into this still undefined condition. Indeed, its diagnosis is currently based on clinical features and the double-blind placebo-controlled gluten challenge [2]. We fully agree with the authors that this diagnostic procedure has some limitations due to its complexity, which could hamper the adherence of the patients. On this basis, we agree with the opinion of Zanini et al. that research for additional biomarkers of NCGS is necessary and compulsory [3]. Therefore, histopathology could represent a very appealing field of study. In this regard, we recently demonstrated, by immunohistochemistry, a rise in CD117+ cells in the lamina propria of patients with NCGS [4]. CD117 may identify mast cells; consequently, this result seems to be in agreement with that of Zanini et al., who found, in most cases, an increase in eosinophil count (more than five eosinophils in the lamina propria per high power field) when compared to the control group, where this finding was absent. These findings seem to lead to a shared conclusion, which might support an additional hypothesis about NCGS pathogenesis: an allergic intolerance to foods other than wheat [5] or a sui generis derangement in immune response could underlie NCGS [6].

In conclusion, we believe that an accurate histological analysis of duodenal samples of NCGS patients could unveil new ideas for its diagnosis [7], but the road is still long, and multicenter blinded studies performed on large population samples are needed.