## 3 Fecal VOC in Gastrointestinal DISEASES
### Inflammatory Bowel Disease and Irritable Bowel Syndrome
In addition, several VOCs were more abundant in UC (i.e., butanoic acid) and IBS (i.e., propanoic acid, indole, dimethyl sulfide and 3 methylbutanoic acid), however, differences were not significant. Furthermore, concentrations of several VOCs in the CD group normalized to \"healthy concentrations\" in the after targeted treatment. In 2014, differences in VOC patterns rather than specific metabolites between 34 adult IBS, 42 CD, 59 UC and 46 HC were assessed using GC with a single metal oxide sensor, coupled to an artificial neural network software [35]. Based on a cross-validation network set, differentiation between IBS and IBD was feasible (Table 3). [PERSON] et al. found outcomes in line with their previous study, in a cohort consisting of 217 adult IBD patients (117 CD, 100 UC) and 109 HC using GC-MS [36]. They found upregulation of three VOCs and downregulation of two VOCs in patients with active CD compared to inactive CD and HC. The model could also discriminate between CD patients with colonic and small bowel localization, but was less accurate in separating active and inactive UC and HC (Table 3). A recent study by [PERSON] et al. investigated the potential of fecal VOCs as novel noninvasive IBD biomarker for adult IBD [37]. In this study, GC with a metal oxide gas sensor and a computer algorithm was used to identify electrical resistance, to compare resistance patterns among 33 adults with active IBD, 50 adults with inactive IBD, 28 adult IBS patients and 41 HC. They demonstrated significant differences between active CD vs. IBS and IBS vs. HC (Table 3). Both the sensitivity and specificity for the discrimination of IBS from HC and IBS from IBD are in line with a previous conducted study by [PERSON] et al. [33]. Over the last few years, pediatric IBD and IBS have also been subject of several fecal VOC studies. In 2014, [PERSON] et al. studied differences in fecal VOC patterns between pediatric de novo treatment-naive IBD patients and 29 HC by means of an eNose (Cyranose 320(r)) at baseline and upon achieving remission (at 6 weeks of follow-up) [38]. Both active UC and CD could be distinguished from healthy controls based on their VOC profiles (Table 3). Upon remission, UC and CD could still be discriminated from HC with high diagnostic accuracy. In addition, CD differed from UC with a high accuracy during active disease and upon clinical remission (Table 3). In a study by [PERSON] et al., VOC patterns of fecal samples from de novo, treatment-naive pediatric IBD patients were compared to 24 matched HC using FAIMS [39]. IBD could be distinguished from HC with a high overall accuracy. In addition, CD could also be differentiated from HC with a high diagnostic accuracy, whereas the diagnostic accuracy to discriminate between UC and HC was moderate (Table 3). Notably, in that study no significant differences were seen between CD and UC, in contrast to the previous study performed by an eNose [38]. This contrast might be explained by the usage of different analytical techniques. Hypothetically, minor differences in VOC profiles as measured by an eNose device may induce significant differences, whereas these differences are not (significantly) detected by FAIMS, and vice versa. Recently, [PERSON] et al. published a study comparing fecal VOC patterns of 15 pediatric IBS patients with 30 de novo, treatment naive IBD patients and 30 HC by means of FAIMS [40]. In line with previous results, IBD could be distinguished from HC with a high diagnostic accuracy. In addition, IBD and IBS could also be discriminated with a high accuracy, whereas no significant differences were found between IBS and HC (Table 3). In summary, all performed studies on fecal VOC analysis in IBD, using both metabolite-specific and pattern-based methods, have confirmed the potential of fecal VOCs as noninvasive biomarkers for IBD detection and even to monitor disease activity. VOC analysis seems to add value to discriminate IBS from IBD, but not from HC.