TY - JOUR
T1 - Fecal Volatile Metabolomics Predict Gram-Negative Late-Onset Sepsis in Preterm Infants
T2 - A Nationwide Case-Control Study
AU - Frerichs, Nina M.
AU - el Manouni el Hassani, Sofia
AU - Deianova, Nancy
AU - van Weissenbruch, Mirjam M.
AU - van Kaam, Anton H.
AU - Vijlbrief, Daniel C.
AU - van Goudoever, Johannes B.
AU - Hulzebos, Christian V.
AU - Kramer, Boris W.
AU - d’Haens, Esther J.
AU - Cossey, Veerle
AU - de Boode, Willem P.
AU - de Jonge, Wouter J.
AU - Wicaksono, Alfian N.
AU - Covington, James A.
AU - Benninga, Marc A.
AU - de Boer, Nanne K.H.
AU - Niemarkt, Hendrik J.
AU - de Meij, Tim G.J.
N1 - Funding Information:
This work was supported by unrestricted grants from the Landelijke Vereniging van Crematoria (Dr. C.J. Vaillant Fonds); Zeldzame Ziekten Fonds and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement [grant number 814168]. None of the funding sources had any role in the design or conduct of the study.
Funding Information:
None of the co-authors received a honorarium, grant, or other form of payment for the production of this manuscript. Outside the submitted work, N.K.H.d.B. has served as a speaker for AbbVie and MSD. He has also served as a consultant and/or principal investigator for TEVA Pharma BV and Takeda. He has received a (unrestricted) research grant from Dr Falk, TEVA Pharma BV, MLDS and Takeda. The other authors have nothing to declare.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/3
Y1 - 2023/3
N2 - Early detection of late-onset sepsis (LOS) in preterm infants is crucial since timely treatment initiation is a key prognostic factor. We hypothesized that fecal volatile organic compounds (VOCs), reflecting microbiota composition and function, could serve as a non-invasive biomarker for preclinical pathogen-specific LOS detection. Fecal samples and clinical data of all preterm infants (≤30 weeks’ gestation) admitted at nine neonatal intensive care units in the Netherlands and Belgium were collected daily. Samples from one to three days before LOS onset were analyzed by gas chromatography—ion mobility spectrometry (GC-IMS), a technique based on pattern recognition, and gas chromatography—time of flight—mass spectrometry (GC-TOF-MS), to identify unique metabolites. Fecal VOC profiles and metabolites from infants with LOS were compared with matched controls. Samples from 121 LOS infants and 121 matched controls were analyzed using GC-IMS, and from 34 LOS infants and 34 matched controls using GC-TOF-MS. Differences in fecal VOCs were most profound one and two days preceding Escherichia coli LOS (Area Under Curve; p-value: 0.73; p = 0.02, 0.83; p < 0.002, respectively) and two and three days before gram-negative LOS (0.81; p < 0.001, 0.85; p < 0.001, respectively). GC-TOF-MS identified pathogen-specific discriminative metabolites for LOS. This study underlines the potential for VOCs as a non-invasive preclinical diagnostic LOS biomarker.
AB - Early detection of late-onset sepsis (LOS) in preterm infants is crucial since timely treatment initiation is a key prognostic factor. We hypothesized that fecal volatile organic compounds (VOCs), reflecting microbiota composition and function, could serve as a non-invasive biomarker for preclinical pathogen-specific LOS detection. Fecal samples and clinical data of all preterm infants (≤30 weeks’ gestation) admitted at nine neonatal intensive care units in the Netherlands and Belgium were collected daily. Samples from one to three days before LOS onset were analyzed by gas chromatography—ion mobility spectrometry (GC-IMS), a technique based on pattern recognition, and gas chromatography—time of flight—mass spectrometry (GC-TOF-MS), to identify unique metabolites. Fecal VOC profiles and metabolites from infants with LOS were compared with matched controls. Samples from 121 LOS infants and 121 matched controls were analyzed using GC-IMS, and from 34 LOS infants and 34 matched controls using GC-TOF-MS. Differences in fecal VOCs were most profound one and two days preceding Escherichia coli LOS (Area Under Curve; p-value: 0.73; p = 0.02, 0.83; p < 0.002, respectively) and two and three days before gram-negative LOS (0.81; p < 0.001, 0.85; p < 0.001, respectively). GC-TOF-MS identified pathogen-specific discriminative metabolites for LOS. This study underlines the potential for VOCs as a non-invasive preclinical diagnostic LOS biomarker.
KW - fecal biomarker
KW - gas chromatography—ion mobility spectrometry
KW - gas chromatography—time of flight—mass spectrometry
KW - microbiota
KW - neonatology
KW - volatile organic compounds
U2 - 10.3390/microorganisms11030572
DO - 10.3390/microorganisms11030572
M3 - Article
AN - SCOPUS:85151481985
SN - 2076-2607
VL - 11
JO - Microorganisms
JF - Microorganisms
IS - 3
M1 - 572
ER -