ABSTRACT
OBJECTIVES: Several studies associated altered gut microbiota composition in preterm infants with late-onset sepsis (LOS), up to days before clinical onset of sepsis. Microbiota analysis as early diagnostic biomarker is, however, in clinical practice currently not feasible because of logistic aspects and high costs. Therefore, we hypothesized that analysis of fecal volatile organic compounds (VOCs) may serve as noninvasive biomarker to predict LOS at a preclinical stage, because VOC reflect the composition and activity of intestinal microbial communities. METHODS: In a prospective multicenter study, fecal samples were collected daily from infants with a gestational age of <30 weeks. VOC signatures of fecal samples from infants with LOS, collected up to 5 days before diagnosis, were analyzed by means of an electronic nose technology (Cyranose 320) and compared to matched controls. RESULTS: Fecal VOC profiles of infants with LOS (nâ=â36) could be discriminated from controls (nâ=â40) at 3 days (area under the curve [±95% confidence interval], P value, sensitivity, specificity; 70.2 [52.2-88.3], 0.033, 57.1%, 61.5%), 2 days (77.7 [62.7-92.7], 0.050, 75.0%, 70.8%), and 1 day (70.4 [49.6-91.3], 0.037, 64.3%, 64.3%) before the onset of LOS. CONCLUSIONS: Fecal VOC profiles of preterm infants with LOS could be discriminated from matched controls, up to 3 days before clinical onset of the disease, underlining the hypothesis that intestinal microbiota may play an etiological role in LOS. Notably, VOC profiling is clinically feasible and the potential of this technique in the early detection of LOS needs to be confirmed in future studies.
Subject(s)
Feces/chemistry , Gastrointestinal Microbiome , Infant, Premature, Diseases/diagnosis , Neonatal Sepsis/diagnosis , Volatile Organic Compounds/metabolism , Biomarkers/metabolism , Case-Control Studies , Electronic Nose , Female , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/metabolism , Infant, Premature, Diseases/microbiology , Male , Neonatal Sepsis/metabolism , Neonatal Sepsis/microbiology , Proof of Concept Study , Prospective StudiesABSTRACT
The diagnostic work-up and follow-up of paediatric functional gastrointestinal disorders and organic conditions usually includes invasive tests, carrying a high burden on patients. There is a place, therefore, for novel, noninvasive disease-specific biomarkers. Volatile organic compounds (VOCs), originating from (patho)physiological metabolic processes in the human body, are excreted as waste products through all conceivable bodily excrements. The spectrum of VOCs harbours a magnificent source of information, with the potential to serve as noninvasive diagnostic biomarkers and to monitor disease activity. VOC analysis has been studied in children and infants with a variety of gastrointestinal diseases, including inflammatory bowel disease, liver diseases, irritable bowel syndrome, necrotizing enterocolitis and infectious diarrhoea. Most of these studies, although limited in sample size, show that patients can be discriminated from controls based on their VOC profiles, underscoring the potential of VOC analysis in diagnosis and follow-up. Currently, however, the application of VOC analysis in clinical practice is limited; substantial challenges, including methodological, biological, and analytical problems, still need to be met. In this review we provide an overview of the available literature on the potential of VOCs as biomarkers for paediatric gastrointestinal diseases. We discuss the available techniques to analyse VOCs and provide topics for VOC-related research, which need to be addressed before VOC diagnostics can be implemented in daily clinical practice.
