Exploring the link between mental health and functional gastrointestinal disorders
2017-03-02T02:56:19Z (GMT) by
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder (FGID) characterised by abdominal pain and associated with altered bowel habits. There is no cure for IBS and treatment is limited to symptom management strategies. Common approaches to control symptoms associated with IBS include pharmacological agents, dietary therapies and psychological treatments. There is high-quality evidence of efficacy for the low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet but the gluten-free diet is also being increasingly applied. In fact, non-coeliac gluten sensitivity (NCGS), defined by the worsening of symptoms when consuming gluten and the improvement of symptoms on a gluten-free diet, is now considered a distinct clinical entity. Psychological treatments are also being increasingly sought but how their efficacy compares with that of dietary approaches is unknown. This thesis contains a series of studies which aimed to 1) gain a greater understanding of the differences, similarities and possible overlap between IBS and NCGS; 2) fill gaps in evidence regarding effects of gluten ingestion on extraintestinal symptoms in patients with NCGS; 3) develop a method for the large-scale isolation of gliadin suitable for human feeding trials; and 4) examine the efficacy of gut-directed hypnotherapy compared to that of the low FODMAP diet. Initial results from a double-blind, placebo-controlled, randomised, cross-over trial in 22 participants were suggestive of gluten-specific changes to current feelings of depression in patients with NCGS but more detailed analysis in a different cohort of patients with NCGS failed to reproduce this effect. Notably, additional investigations showed no evidence of gluten-specific worsening of any psychological indices, quality of life, fatigue or gastrointestinal symptoms. The only exception was a small increase in response times on the Subtle Cognitive Impairment Test (SCIT). Overall, these studies failed to support a specific entity of NCGS in patients who would otherwise be classified as having IBS or another FGID. A method for the large-scale isolation of gliadin suitable for human consumption was successful. However, the lack of specific gluten-mediated effects precluded the planned study of purified gliadin in defining its role in symptom induction in patients with NCGS. How effective psychological therapies might be for IBS was addressed in a randomised un-blinded study in 78 participants with IBS comparing the relative efficacy of gut-directed hypnotherapy with that of the more established ‘gold standard’, the low FODMAP diet, alone or in combination. In terms of effect on gastrointestinal symptoms and quality of life, both therapies were similarly efficacious over 6 months, but without additive effects. Gut-directed hypnotherapy had additional psychological benefits. These results indicate that gut-directed hypnotherapy should be considered a viable modality and applied as a primary therapy for patients with IBS. In conclusion, this thesis has made a considerable contribution to our understanding of the association between psychological health and FGID and has fulfilled its aims. First, it provides high-quality evidence that gluten ingestion is unlikely to be associated with the worsening of psychological (or gastrointestinal) manifestations in patients with self-reported NCGS and questions the existence of the latter as a specific entity. Secondly, a procedure was developed to enable future study of the responsible moiety for gluten-mediated effects. Thirdly, it provides compelling evidence that gut-directed hypnotherapy is a viable therapeutic option for the treatment of IBS. Further research into mechanisms of action and predictors of response, as well as subtle effects of gluten on cognition, is warranted.