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Role of naturally occurring dietary salicylates in irritable bowel syndrome (IBS)
thesisposted on 23.02.2017, 23:24 by Malakar, Sreepurna
Most patients with irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, blame food as the causative agent for symptoms. Most attention has been on poorly-absorbed carbohydrates and gluten, but naturally-occurring bioactive food chemicals like salicylates (SA) have also been suggested to induce symptoms or even cause IBS. Population surveys have related the synthetic SA, ASA, to IBS and some authors have claimed that dietary SA causes symptoms in 70%. However, the potential role of dietary SA in IBS via randomized controlled trials remains unexplored, hampered by limited and controversial data on SA content of foods in current literature, preventing formulation of proper dietary strategies. Currently, ASA-sensitivity is detected by oral ASA provocation challenge. Food SA sensitivity is detected by lengthy and highly restrictive ‘elimination-rechallenge’ procedures. An in vitro assay, the basophil activation test (BAT), used routinely for detecting IgE-mediated hypersensitivities, is suggested to reliably detect food chemical sensitivities, but results remain controversial. This thesis aimed to address the three above-mentioned gaps in evidence. First, state-of-art methodology underpinned by highly sensitive gas chromatography-mass spectrometry (GC-MS) was developed and validated to accurately determine SA content of more than 100 foods with meticulous consideration to proper sampling technique, internal standards, varietal and growing conditions. SA content detected mostly varied from previous literature; for example, beetroot contained 26.96 mg/kg compared to 1.8 mg/kg reported previously. Secondly, food analysis data enabled construction of high-/low-SA diets for a pilot double-blind, randomized, crossover study to assess dietary tolerability and understand if dietary SA is associated with IBS symptoms. Ten patients were fed majority of foods for two 2-week periods (with washout between). Symptom responses were compared using visual analogue scales. The diets were well tolerated. No difference in symptoms between high and low SA diets were found, except in one patient with ASA-induced urticaria (in whom abdominal symptoms were markedly worse on the high SA diet) and another with only IBS. Thirdly, the vexing issue of identifying subjects with SA sensitivity was addressed by evaluating performance of the BAT in healthy subjects and in known or suspected SA-sensitive patients. No differences in basophil activation (IgE+/CD63+) were detected between the groups over a range of SA concentrations (P-values >0.50). In conclusion, detailed methodology with GC-MS was validated for determination of food SA content, with disagreement on content compared to previous methodologies. A wider range of foods need analysis for long-term sustainable dietary strategies. Evidence for SA-associated abdominal symptoms in two IBS patients were found, of which one had known ASA-sensitivity. Since the BAT was unable to identify SA-sensitive patients, the low prevalence of dietary SA-sensitivity in this small cohort would suggest a non-targeted low-SA dietary approach for IBS patients will have little clinical impact. Evaluation of larger ASA-sensitive IBS and IBS populations is warranted to define clinical predictors of response and role of reducing dietary SA intake in clinical practice. In addition, the step-wise methodological approach developed in this thesis could be applied to examine other bioactive food chemicals that putatively induce abdominal symptoms in IBS patients.