Reply

Abstract

The letter from Carroccio et al1Carroccio A. et al.Gastroenterology. 2014; 146: 320-321Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar raises several important issues and we will address them in sequence. First, it is likely that the 2-week run-in period during which FODMAPs were reduced2Biesiekierski J.R. et al.Gastroenterology. 2013; 145: 320-328Abstract Full Text Full Text PDF PubMed Scopus (629) Google Scholar may have led to changes in the microbiota of the intestine, as recently reported after 4 weeks' exposure to dietary restriction of FODMAPs.3Staudacher H.M. et al.J Nutr. 2012; 142: 1510-1518Crossref PubMed Scopus (430) Google Scholar It is possible that such changes may be one reason for a loss of a positive response to gluten. However, it must be stressed that the role of microbiota in the pathogenesis of irritable bowel syndrome is speculative. What is good and what is not, and whether changes are secondary or primary to intestinal conditions remain to a large extent unresolved for most intestinal conditions rather than being established as ‘crucial’. We agree that microbiota should be one part of the puzzle to be teased out in studies in which diet is being manipulated. Secondly, we have difficulty with the suggestion that patients with evidence of immune activation in the duodenum should be included in a study of non-celiac gluten sensitivity (NCGS). Such changes might represent celiac disease or hypersensitivity reactions to wheat-associated proteins in some patients. The current definition of NCGS encompasses the exclusion of both celiac disease and immune responses to wheat proteins.4Ludvigsson J.F. et al.Gut. 2012; 62: 43-52Crossref PubMed Scopus (1125) Google Scholar Given the early stages in our understanding of the NCGS entity, we believe we should strictly keep to this definition to ensure findings do not overlap with other conditions. We do agree, however, that a study with similar design to ours should be directed towards the patients with duodenal intraepithelial lymphocytosis as this is a different group to those with normal duodenal pathology. Thirdly, we also have problems with the proposal that our data suggest circulating antibodies to whole gliadin could be a biomarker for patients with NCGS. While they were detected in one-third of the patients in our study, it is untenable to use this test as a biomarker for NCGS when none of the cohort studied demonstrated specific symptomatic reactions to gluten. In fact the opposite seems more logical. We trust we have not misconstrued the meaning of the suggestion made. Fourthly, as evidenced by our study design, we too were concerned that we had identified patients who had reactions to whey proteins. However, all the positive reactions occurred within the first two days of exposure and very few were specific to whey. In the second challenge, it would be anticipated that reactions to a similar dose of whey would occur again quickly, especially if immune reactions are the basis for the symptom induction. It is important also to point out that the rate of placebo responses is a major difference between our findings,2Biesiekierski J.R. et al.Gastroenterology. 2013; 145: 320-328Abstract Full Text Full Text PDF PubMed Scopus (629) Google Scholar, 5Biesiekierski J.R. et al.Am J Gastroenterol. 2011; 106: 508-514Crossref PubMed Scopus (600) Google Scholar and observations of other groups6Ford A.C. et al.Aliment Pharmacol Ther. 2010; 32: 144-158Crossref PubMed Scopus (161) Google Scholar with those in published reports from Carroccio et al.7Carroccio A. et al.Am J Gastroenterol. 2012; 107: 1898-1906Crossref PubMed Scopus (350) Google Scholar We find placebo responses commonly in contrast to the rare occurrence in the hands of Carroccio et al.7Carroccio A. et al.Am J Gastroenterol. 2012; 107: 1898-1906Crossref PubMed Scopus (350) Google Scholar Reasons for such differences in experience are not clear. The final suggestion of renaming NCGS as NCWS (not-celiac wheat sensitivity) is intriguing. However, it has 1 major flaw. It would also include symptom induction by short-chain carbohydrates such as fructans and galacto-oligosaccharides in wheat. The term would then have to apply to about 75% of patients with functional intestinal symptoms.8Shepherd S.J. et al.J Am Diet Assoc. 2006; 106: 1631-1639Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar Thus, this label, like NCGS, would not clarify the puzzle and would overcomplicate an already confusing field of nomenclature.4Ludvigsson J.F. et al.Gut. 2012; 62: 43-52Crossref PubMed Scopus (1125) Google Scholar Non-Celiac Wheat Sensitivity Is a More Appropriate Label Than Non-Celiac Gluten SensitivityGastroenterologyVol. 146Issue 1PreviewWe have read with great interest the article by Biesiekirski et al,1 in which a double-blind, placebo-controlled (DBPC) rechallenge study demonstrated a lack of evidence of specific or dose-dependent effects of gluten in patients with non-celiac gluten sensitivity (NCGS) while on a low FODMAP diet. The authors themselves noted that these data are inconsistent with their previous study,2 and considered the strict control on the patients' diet throughout the entire study a pivotal difference. During the new study, all patients consumed a diet including foods with low FODMAP content and this led to an immediate improvement of the irritable bowel syndrome (IBS) symptoms, irrespective of the successive gluten challenges. Full-Text PDF