Does Non-Coeliac Gluten Sensitivity Exist?

Introduction: Coeliac disease (CD) is a gluten-sensitive enteropathy which affects 1% of the population. The treatment for CD is a strict lifelong gluten-free diet (GFD). IgE-wheat allergy is another gluten-related disorder affecting 0.1-1% of children, although most will have outgrown the condition by adulthood. However, recent media reports suggest increasing popularity and consumption of a GFD even in the absence of CD or IgE-wheat allergy. This has led to the evolution of a newly-defined clinical entity termed non-coeliac gluten sensitivity (NCGS). The aim of this thesis was to determine the existence and characteristics of NCGS. Methods: We ascertained whether there has been a change in awareness of gluten-related disorders amongst the general public and chefs in Sheffield, United Kingdom. The population prevalence of self-reported gluten-sensitivity and the use of a GFD were also determined, as well as the characteristics and diagnostic outcomes in those patients referred to adult secondary-care gastroenterology practice. Finally, we evaluated whether a GFD is being used independently by inflammatory bowel disease (IBD) patients and also if a GFD can be used to treat patients with diarrhoea-predominant irritable-bowel syndrome (D-IBS) previously naive to the effects of gluten. Results: i) There has been a dramatic rise in both the publics’ and chefs’ awareness of gluten-related disorders over a ten-year period. ii) On questioning 1002 community adults, 13% self-reported gluten-sensitivity with 3.7% consuming a GFD yet only 0.8% having a doctor-diagnosis of CD. Subjects self-reporting gluten-sensitivity were predominantly young to middle-aged women and had a greater prevalence of IBS. Further, a combination of intestinal and extra-intestinal symptoms were described in relation to gluten ingestion; these include abdominal pain/discomfort, bloating and altered bowel habit (consistent with the criteria used to define IBS), as well as fatigue, headaches, depression, skin rash, and joint pains. On evaluating 200 patients referred to secondary-care with self-reported gluten sensitivity, 7% were found to have CD with the remaining 93% classed as self-reported NCGS. Analysis of those with NCGS suggested that 98.5% could be dietary-related IBS. However, 1.5% were found to have IBD with such patients having demonstrated alarm symptoms and/or abnormal systemic inflammatory markers that necessitated colonic investigations. iii) We then separately established that patients with IBD who self-report NCGS are more likely to have severe or stricturing disease compared to IBD patients who do not report gluten sensitivity. iv) Finally, in D-IBS patients previously naive to the effects of gluten a six-week trial of a GFD led to clinical improvement in 71% of cases. Furthermore, 72% opted to continue with a GFD thereafter and at 18-month mean follow-up were still taking the diet, maintained symptom improvement, and demonstrated similar anthropometric/biochemical status relative to baseline. We identified that the benefits of a GFD in D-IBS subjects may differ according to the presence or absence of HLA-DQ2/8 genotype. Conclusion: We have demonstrated that self-reported NCGS does exist. The condition is associated with IBS, although it can rarely be present in IBD. A GFD can be a treatment option in D-IBS patients previously naive to the effects of gluten. This body of work has significantly contributed towards our understanding of NCGS. However, as with most research projects it has instigated further questions that require exploration.