Zsa Zsa Weerts

General discussion 239 10 General discussion In this thesis, we have focused on the diagnostic criteria, targeted treatment, and socioeconomic burden of irritable bowel syndrome (IBS). We showed that patients who fulfill the updated and more restrictive Rome IV criteria are more likely to be younger women, with more severe gastrointestinal (GI) symptomatology, more severe psychological comorbidities, and lower quality of life, compared to patients with similar symptoms who do did not fulfill the Rome IV criteria ( chapter 2 ). In chapter 3 , we found that 30% of patients did no longer fulfill the Rome III criteria for IBS after a follow- up period of five years. However, this reduction in GI symptoms was not paralleled by improvement in quality of life or life satisfaction. Our data suggest that quality of life and general well-being are more related to concurrent anxiety and depression scores than to GI symptom severity. To further improve patient outcome and quality in life in IBS, better and possibly more targeted treatments are needed. In chapter 4 , we provided a comprehensive overview of transient receptor potential channels as novel treatment strategies in patients with IBS. Transient receptor potential melastatin 8 (TRPM8) is of particular interest because menthol, the primary constituent of peppermint oil, is an agonist for the TRPM8 receptor. Peppermint oil itself is a commonly used therapeutic agent in IBS. In chapter 5 , we therefore focused more specifically on the TRPM8 channel and explored neuro-immune interactions possibly underlying symptom generation in IBS. By using various experimental techniques, we shed light on the potential anti-inflammatory function of TRPM8 in IBS. Because of a relative lack in high-quality evidence for efficacy of peppermint oil, we went on to further evaluate the clinical performance of peppermint oil in IBS. First, in chapter 6 , we demonstrated that a newly developed ileocolonic release peppermint oil formulation had a significantly later mean peak menthol concentration in the blood, in comparison with the conventional small-intestinal release peppermint oil. This finding points to a more distal, presumably ileocolonic, release of peppermint oil in the intestine when given in the ileocolonic release peppermint oil formulation. Thereafter, in chapter 7 , we investigated the efficacy and safety of small-intestinal and ileocolonic release peppermint oil in patients with IBS in a large multicenter randomized controlled trial, the PERSUADE study. We found that peppermint oil, in both formulations, was not superior compared to placebo when using the FDA recommended primary outcome of abdominal pain response. Small-intestinal release peppermint oil, however, showed significant improvements in secondary outcomes of IBS symptoms. We also showed that small-intestinal peppermint oil appears to be cost-effective in patients with IBS during an eight-week treatment period ( chapter 8 ). In the final chapter, chapter 9 ,