Daniel J C Berkhout1, Hendrik J Niemarkt, Martin Buijck, Mirjam M van Weissenbruch, Paul Brinkman, Marc A Benninga, Anton H van Kaam, Boris W Kramer, Peter Andriessen, Nanne K H de Boer, Tim G J de Meij. 1. *Department of Pediatric Gastroenterology, VU University Medical Center †Department of Pediatric Gastroenterology, Emma Children's Hospital/Academic Medical Center, Amsterdam ‡Neonatal Intensive Care Unit, Máxima Medical Center, Veldhoven §Neonatal Intensive Care Unit, VU University Medical Center ||Department of Respiratory Medicine, Academic Medical Center ¶Neonatal Intensive Care Unit, Emma Children's Hospital/Academic Medical Center, Amsterdam #Department of Pediatrics, Maastricht University Medical Center, Maastricht **Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
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 (n = 36) could be discriminated from controls (n = 40) 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.
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 (n = 36) could be discriminated from controls (n = 40) 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.
Authors: Daniel J C Berkhout; Hendrik J Niemarkt; Marc A Benninga; Andries E Budding; Anton H van Kaam; Boris W Kramer; Charlene M Pantophlet; Mirjam M van Weissenbruch; Nanne K H de Boer; Tim G J de Meij Journal: Pediatr Res Date: 2017-11-22 Impact factor: 3.756
Authors: Daniel J C Berkhout; Marc A Benninga; Ruby M van Stein; Paul Brinkman; Hendrik J Niemarkt; Nanne K H de Boer; Tim G J de Meij Journal: Sensors (Basel) Date: 2016-11-23 Impact factor: 3.576
Authors: Christopher J Stewart; Nicholas D Embleton; Emma C L Marrs; Daniel P Smith; Tatiana Fofanova; Andrew Nelson; Tom Skeath; John D Perry; Joseph F Petrosino; Janet E Berrington; Stephen P Cummings Journal: Microbiome Date: 2017-07-12 Impact factor: 14.650
Authors: Nancy Deianova; Sofia El Manouni El Hassani; Hendrik J Niemarkt; Veerle Cossey; Anton H van Kaam; Floor Jenken; Mirjam M van Weissenbruch; Esmee M Doedes; Kyra Baelde; Renee Menezes; Marc A Benninga; Wouter J de Jonge; Nanne K de Boer; Tim G de Meij Journal: Biosensors (Basel) Date: 2020-05-11
Authors: Sofia El Manouni El Hassani; Ruud J Soers; Daniel J C Berkhout; Hendrik J Niemarkt; Hans Weda; Tamara Nijsen; Marc A Benninga; Nanne K H de Boer; Tim G J de Meij; Hugo H Knobel Journal: Metabolomics Date: 2020-10-10 Impact factor: 4.290
Authors: Sofia El Manouni El Hassani; Hendrik J Niemarkt; Hager Said; Daniel J C Berkhout; Anton H van Kaam; Richard A van Lingen; Marc A Benninga; Nanne K H de Boer; Tim G J de Meij Journal: Sensors (Basel) Date: 2018-09-11 Impact factor: 3.576
Authors: Sofie Bosch; Sofia El Manouni El Hassani; James A Covington; Alfian N Wicaksono; Marije K Bomers; Marc A Benninga; Chris J J Mulder; Nanne K H de Boer; Tim G J de Meij Journal: Anal Chem Date: 2018-06-15 Impact factor: 6.986