Sofia El Manouni El Hassani1, Hendrik J Niemarkt2, Daniel J C Berkhout1, Carel F W Peeters3, Christian V Hulzebos4, Anton H van Kaam5,6, Boris W Kramer7, Richard A van Lingen8, Floor Jenken9, Willem P de Boode10, Marc A Benninga1, Andries E Budding11, Mirjam M van Weissenbruch5, Nanne K H de Boer12, Tim G J de Meij1. 1. Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Emma Children's Hospital, Department of Pediatrics, Amsterdam, The Netherlands. 2. Neonatal Intensive Care Unit, Máxima Medical Center, Veldhoven, The Netherlands. 3. Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands. 4. Neonatal Intensive Care Unit, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands. 5. Neonatal Intensive Care Unit, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands. 6. Neonatal Intensive Care Unit, Amsterdam UMC, Academic Medical Center, Amsterdam, The Netherlands. 7. Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands. 8. Neonatal Intensive Care Unit, Amalia Children's Centre/Isala, Zwolle, The Netherlands. 9. Neonatal Intensive Care Unit, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands. 10. Department of Microbiology, Neonatal Intensive Care Unit, Amalia Children's Hospital, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. 11. inBiome BV, Amsterdam, The Netherlands. 12. Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Abstract
BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker.
BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker.
Authors: Fleur M Keij; Niek B Achten; Gerdien A Tramper-Stranders; Karel Allegaert; Annemarie M C van Rossum; Irwin K M Reiss; René F Kornelisse Journal: Front Pediatr Date: 2021-04-01 Impact factor: 3.418