Fecal microbiota and metabolomics as preclinical diagnostic biomarkers in neonatal microbiome-driven diseases

This thesis focusses on the potential of gut microbiota and fecal volatile organic compounds (VOC) as novel preclinical biomarkers for microbiome-driven neonatal diseases. Fecal volatile organic compounds are hypothesized to reflect the function of the gut microbiota, host and interaction between both. Previous studies have demonstrated that preterm infants who developed late onset sepsis (LOS), can be differentiated from non-LOS cases based on their fecal VOC profile. In this thesis, it has been demonstrated that LOS cases can be differentiated from controls based on their gut microbiota composition in a preclinical phase. Necrotizing enterocolitis (NEC), a devastating gastro-intestinal disease, occurring in preterm infants, could also be differentiated from controls based on their fecal VOC profiles and microbiota composition. This difference was mostly profound in severe NEC. Before clinical implementation of fecal VOC as preclinical biomarker, a uniform analytical protocol should be developed. Therefore, potential influencing factors on fecal VOC outcome were assessed. This thesis proposes an analytical protocol for fecal VOC analysis in preterm born infants.