Zsa Zsa Weerts

Addendum 268 Impact on research This thesis is relevant for researchers in the field of functional gastrointestinal disorders. After redefinition of the diagnostic criteria our results were one of the first to show how this affected prevalence and characteristics of IBS patient populations. In addition, the studies included in this thesis provide a solid basis to optimize treatment response measurement in functional GI disorders by designing and describing a framework for digitalized data-collection in RCTs. This data-collection method showed excellent adherence from both patients and researchers in our PERSUADE study. In addition, future Dutch studies benefit from the national multicenter network established at the start of our peppermint oil RCT. Currently, the (slightly adapted) framework for data-collection is being used for symptom measurement in the multicenter RCT of our research group on the efficacy of face-to-face versus online hypnotherapy for patients with IBS. This thesis has contributed to science by giving an overview of current knowledge on transient receptor potential channels and by investigating the role of the TRPM8 receptor in the human (IBS) colon. The results in this thesis showed for first time that colonic mRNA expression levels are significantly higher in patients with IBS compared to healthy volunteers and that intestinal TRPM8 activation results in a decrease of pro- inflammatory cytokines. Shedding light onto this pathophysiological mechanism may lead to the proposal of new mechanistic studies of which the outcomes can eventually lead to the development of more targeted treatment for patients with IBS. Impact on patients with IBS and society Importantly, the research topics described in this thesis provide benefit to patients with IBS in a broad sense. By increasing knowledge on key factors involved in pathophysiology of IBS and in quality of life, more targeted treatment can be developed and investigated. This will then hopefully lead to improvements in healthcare with better health outcomes on the long-term for patients with IBS. Although there is long-standing appreciation for the magnitude of the societal and economic burden imposed by IBS, Dutch data are still sparse. Data included in this thesis indicated that a large part of the substantial healthcare costs incurred by Dutch patients with IBS was actually driven by mental and not GI-related healthcare. In addition, it was shown that patients who improve in GI symptom severity did not necessarily have a better quality of life. These findings point to a large impact of