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Hadjivassiliou M, Sanders DS, Gr€ unewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol 2010; 9: 318–30. 13. Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology 2013; 144: 903–11.e3. 14. Morken MH, Lind RA, Valeur J, Wilhelmsen I, Berstad A. Subjective health complaints and quality of life in patients with irritable bowel syndrome following Giardia lamblia infection: a case control study. Scand J Gastroenterol 2009; 44: 308–13. 15. Verdu EF, Armstrong D, Murray JA. Between celiac disease and irritable bowel syndrome: the “no man’s land” of gluten sensitivity. Am J Gastroenterol 2009; 104: 1587–94. Editorial: noncoeliac gluten sensitivity – a disease of the mind or gut? Authors’ reply S. L. Peters*, J. R. Biesiekierski † , G. W. Yelland* ,‡ , J. G. Muir* & P. R. Gibson* ,† *Department of Gastroenterology, Central Clinical School, Monash University, The Alfred Hospital, Melbourne, Vic, Australia. † Department of Gastroenterology, Eastern Health Clinical School, Monash University, Box Hill, Vic, Australia. ‡ School of Health Sciences, RMIT University, Bundoora, Vic, Australia. E-mail: simone.peters@monash.edu doi:10.1111/apt.12805 We thank Aziz et al. for their thoughtful commentary on our recent article. 1, 2 They raise important issues, of which we would agree, with a few qualifying state- ments. No studies have been performed to show that gluten is the cause of depression or its improvement. However, psychiatric symptoms are known to be common in many chronic health conditions. In coeliac disease, anxiety and depression are typical in untreated patients, and improvement in mental state is often shown following gluten withdrawal. 3, 4 The idea that our findings mimic those in coeliac dis- ease does not take this nonspecific effect of illness into account. We can find no studies in the literature that implicate gluten as the causative agent of depression in coeliac disease. This improvement in psychological func- tioning may be the result of symptomatic resolve and enhanced perception of health and psychological well- being. 5 In contrast, the induction of current feelings of depression following the consumption of gluten in this study points to a causative (not associative) role of glu- ten on mental state. The mechanistic action by which gluten might induce these changes in noncoeliac gluten sensitivity (NCGS) remains unknown. While it was hy- pothesised that gluten may induce depression as a con- sequence of changes in brain serotonin, gluten exorphins or changes in gut microbiota, we believe that it was unli- kely to be via the induction of low-grade gut inflamma- tion or changes in intestinal permeability. No changes to any biomarkers of these events were identified in this or previous well controlled studies, 6, 7 although duodenal biopsies were not performed after challenges with gluten or placebo. We wholeheartedly agree with Aziz et al. regarding the limitations of this study. Only a relatively small number of patients were studied and psychological end-points were limited to one scale. The association between gluten-specific acute changes in current feel- ings of depression requires a larger and more detailed examination. Only with clinical trials that include increased duration of gluten exposure, expansion of psychological, and other, end-points and adequate power will it be determined whether gluten does have 114 Aliment Pharmacol Ther 2014; 40: 113-116 ª 2014 John Wiley & Sons Ltd Invited Editorials Alimentary Pharmacology and Therapeutics