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Rome III versus Rome IV criteria for IBS 39 2 With regards to GI symptoms, Rome IV-positive versus -negative subjects reported higher scores in the end-of-day diary for all symptoms assessed ( i.e. abdominal pain, abdominal discomfort, abdominal bloating, flatulence, constipation and diarrhea) and higher symptom scores for all five GSRS-domains, however, this was not statistically significant for indigestion syndrome. Furthermore, Rome IV-positive subjects showed a higher percentage of depressive (21.0% vs. 5.9%, P <0.001) as well as anxiety (37.6% vs. 21.6%, P <0.05) symptoms and lower physical composite scores (41.67 vs. 49.92, P <0.001) with regards to quality of life. Mental composite scores of SF-36 did not show a significant difference between the groups. Results are shown in Table 2.1 . IBS according to Rome IV criteria – Definition 2: Abdominal pain score ≥3 When using the surrogate Rome IV criteria as defined by at least one day of abdominal pain each week using the cut-off for abdominal pain severity of ≥3, of the 404 IBS subjects diagnosed by Rome III criteria, 249 (61.6%) were Rome IV-positive. In line with the findings above, i.e. regarding the cut-off of abdominal pain severity of ≥2, Rome IV-positive subjects were more often female, younger, recruited from secondary/tertiary care, more often hypersensitive on rectal barostat, showed higher symptom severity scores for all symptoms assessed in the end-of-day symptom diary and showed higher percentages of depressive as well as anxiety symptoms compared to Rome IV-negative subjects, when using the cut-off of ≥3. Likewise, subtype distribution ( i.e. based on Rome III criteria) did not differ between the groups. Moreover, with regard to symptom severity on GSRS, Rome IV-positive versus - negative subjects scored significantly higher on all domains including indigestion syndrome when using the cut-off of ≥3. Furthermore, Rome IV-positive subjects scored significantly lower on both physical composite score and mental composite score of SF- 36 compared to Rome IV-negative subjects. Results are shown in Table 2.1 . Alternative Rome IV diagnoses in Rome IV-negative (IBS) subjects Of the Rome IV-negative (IBS) subjects, according to the surrogate Rome IV criteria using the cut-off for abdominal pain severity of ≥3, 34 (23.61%) fulfilled surrogate Rome IV-criteria for functional constipation, 50 (34.25%) for functional diarrhea and 37 (25.69%) for functional abdominal bloating/distension. Results are shown in Table S2.2 .