## 3 Fecal VOC in Gastrointestinal DISEASES  
### Infectious Diseases  
The gold standard for identification of pathogens in infectious diseases comprises of microbiological culture, in specific cases combined with detection of either bacterial DNA, bacterial antigens or microbial toxins. However, results of culture are commonly obtained after at least 48 h, while rapid diagnosis is necessary to apply appropriate therapeutic interventions, such as prescription of targeted antibiotics and isolation of patients [18]. Most studies on application of fecal VOC analysis in infectious disease have focused on _Clostridium difficile_[19; 20; 21; 22; 23]. Other studies include detection of _Campylobacter jejuni_, cholera, giardiasis and rotavirus [21; 23; 24; 25; 26]. _Clostridium difficile_ infection is particularly prevalent in elderly and in patients who have received antimicrobial agents. This infectious disease is highly contagious and development of more severe forms have emerged. Outbreak in hospitals have resulted in ward closures and extensive infection control measures. Rapid diagnosis of _C. difficile_ infection can lead to quick application of therapeutic and hygienic/preventive strategies [27]. [PERSON] and colleagues assessed differences in fecal VOC profiles of 43 _C. difficile_ negative stool samples and 35 _C. difficile_ positive stool samples of adults, with a subdivision in presence of toxins, by means of FAIMS. In addition, the diagnostic accuracy of FAIMS for direct detection of _C. difficile_ in stool samples was determined. Analysis by FAIMS allowed for differentiation of _C. difficile_ positive and negative stool samples (Table 2) [28]. To date, four studies assessed fecal VOC composition in _C. difficile_ positive stool compared to controls by means of GC-MS. One of these studies demonstrated abundance of three VOCs, which were found to be discriminant between _C. difficile_ positive and negative stool samples (Table 2). Unique in this study was usage of enzyme specific substrate, 3-fluoro-hydroxyphenylacetate acid, which is converted by an enzyme produced by _C. difficile_ to the VOC 2-fluoro-4-methylphenol. Addition of this substrate resulted in a high sensitivity and specificity (Table 2). In absence of 2-fluoro-4-methylphenol, discrimination was not possible between _C. difficile_ positive and negative samples [20]. In addition, three other studies demonstrated that, by means of GC-MS, _C. difficile_ positive fecal samples could be distinguished from controls based on their VOC profiles. Specific VOCs, sensitivity and specificity are listed in Table 2[19; 21; 23]. These studies underline the potential of fecal VOC analysis for detection of _C. difficile_, although a uniform VOC profile for _C. difficile_ is yet to be identified. Advantage of VOC targeted diagnostics over culture include opportunities for rapid, bedside detection of _C. difficile_, allowing for timely initiation of therapy and hygienic/preventive strategies. However, additional studies on standardization of sampling methods and assessment of environmental factors are needed, especially the influence of dietary intake on fecal VOC composition, since these effects are still largely unknown, hampering