{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:47:33Z","timestamp":1783090053520,"version":"3.54.6"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Landelijke Vereniging van Crematoria (Dr. C.J. Vaillant Fonds)","award":["814168"],"award-info":[{"award-number":["814168"]}]},{"name":"Zeldzame Ziekten Fonds and the European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie grant agreement","award":["814168"],"award-info":[{"award-number":["814168"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>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 (\u226430 weeks\u2019 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\u2014ion mobility spectrometry (GC-IMS), a technique based on pattern recognition, and gas chromatography\u2014time of flight\u2014mass 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 &lt; 0.002, respectively) and two and three days before gram-negative LOS (0.81; p &lt; 0.001, 0.85; p &lt; 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.<\/jats:p>","DOI":"10.3390\/microorganisms11030572","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T03:37:20Z","timestamp":1677209840000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Fecal Volatile Metabolomics Predict Gram-Negative Late-Onset Sepsis in Preterm Infants: A Nationwide Case-Control Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3568-863X","authenticated-orcid":false,"given":"Nina M.","family":"Frerichs","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"el Manouni el Hassani","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Deianova","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8086-9552","authenticated-orcid":false,"given":"Mirjam M.","family":"van Weissenbruch","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Amsterdam Reproduction and Development Research Institute, Emma Children\u2019s Hospital, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton H.","family":"van Kaam","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Amsterdam Reproduction and Development Research Institute, Emma Children\u2019s Hospital, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-7386","authenticated-orcid":false,"given":"Daniel C.","family":"Vijlbrief","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University Medical Center Utrecht, Wilhelmina Children\u2019s Hospital, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-1703","authenticated-orcid":false,"given":"Johannes B.","family":"van Goudoever","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-7501","authenticated-orcid":false,"given":"Christian V.","family":"Hulzebos","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Beatrix Children\u2019s Hospital, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris. W.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther J.","family":"d\u2019Haens","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Isala Hospital, 8025 AB Zwolle, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Cossey","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem P.","family":"de Boode","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Radboud UMC, Amalia Children\u2019s Hospital, 6525 XZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3241-1547","authenticated-orcid":false,"given":"Wouter J.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0425-1678","authenticated-orcid":false,"given":"Alfian N.","family":"Wicaksono","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Warwick, Coventry CV4 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-6488","authenticated-orcid":false,"given":"James A.","family":"Covington","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Warwick, Coventry CV4 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Benninga","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Emma Children\u2019s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanne K. H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-7208","authenticated-orcid":false,"given":"Hendrik J.","family":"Niemarkt","sequence":"additional","affiliation":[{"name":"Department of Neonatology, M\u00e1xima Medical Center, 5504 DB Veldhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim G. 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