Early empiric antibiotic exposure affects gut microbiota development of very preterm infants

Aranka J. van Wesemael; Kelly Klomp; Anna M. Malinowska; Anton H. van Kaam; Tim G. J. de Meij; Clara Belzer; Hendrik J. Niemarkt; Chris H. P. van den Akker; Rimke R. de Kroon; Nina M. Frerichs; Nathalie J. Oldenburger; Marlou M. A. Kouwenberg-Raets; Christian V. Hulzebos; Esther D'Haens; Willem P. de Boode; Marijn J. Vermeulen; Daniel C. Vijlbrief; Veerle Cossey; Generation P study group

doi:10.1038/s41390-026-04778-y

Early empiric antibiotic exposure affects gut microbiota development of very preterm infants

Aranka J. van Wesemael
, Kelly Klomp
, Anna M. Malinowska
, Anton H. van Kaam
, Tim G. J. de Meij
, Clara Belzer
, Hendrik J. Niemarkt^*
, Chris H. P. van den Akker
, Rimke R. de Kroon
, Nina M. Frerichs
, Nathalie J. Oldenburger
, Marlou M. A. Kouwenberg-Raets
, Christian V. Hulzebos
, Esther D'Haens
, Willem P. de Boode
, Marijn J. Vermeulen
, Daniel C. Vijlbrief
, Veerle Cossey
, Generation P study group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: After birth, antibiotics are frequently administered to preterm infants for suspected early onset sepsis (EOS). Early empiric antibiotic exposure (EEAE) may disrupt the gut microbiota of preterm infants. This study investigates the association between EEAE duration and gut microbiota dynamics in the first month of life in very preterm infants. Methods: A selected cohort of 127 very preterm infants (<30 weeks gestation) without antibiotic exposure after the first week of life, was stratified into 3 EEAE groups: non (n = 36), short (48–96 h; n = 56), and long-exposed (96–192 h; n = 35). Microbiota composition was analyzed by 16S rRNA gene amplicon sequencing of fecal samples collected at week 1–4. Results: EEAE duration was associated with increased alpha-diversity over time. Veillonella and Enterococcus were significantly lower in EEAE groups compared to non-exposed infants. Four microbial community types (CTs) were identified independent of antibiotic duration. Both EEAE groups had a higher prevalence of the Staphylococcus CT. Conclusion: Both short and long EEAE are associated with changes in the preterm gut microbiota, impacting alpha-diversity, taxonomic composition, and one community type’s prevalence in the first month of life. These findings underscore the impact of antibiotic initiation for suspected EOS on the preterm gut microbiota. Impact: This multicenter cohort study investigates the impact of early empiric antibiotic exposure in very preterm infants on the gut microbiota during the first month of life. It includes a unique control group of infants without any antibiotic exposure. It shows both short and long early empiric antibiotic exposure affects the gut microbiota diversity, composition, and community type during the first month of life. Efforts aimed at reducing the initiation of early empirical antibiotic treatment in very preterm infants with suspected early-onset sepsis may help mitigate disruptions to the developing gut microbiota.

Original language	English
Number of pages	11
Journal	Pediatric Research
DOIs	https://doi.org/10.1038/s41390-026-04778-y
Publication status	E-pub ahead of print - 2026

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van Wesemael, A. J., Klomp, K., Malinowska, A. M., van Kaam, A. H., de Meij, T. G. J., Belzer, C., Niemarkt, H. J., van den Akker, C. H. P., de Kroon, R. R., Frerichs, N. M., Oldenburger, N. J., Kouwenberg-Raets, M. M. A., Hulzebos, C. V., D'Haens, E., de Boode, W. P., Vermeulen, M. J., Vijlbrief, D. C., Cossey, V., & Generation P study group (2026). Early empiric antibiotic exposure affects gut microbiota development of very preterm infants. Pediatric Research. Advance online publication. https://doi.org/10.1038/s41390-026-04778-y

@article{2469a3d23c7144ff89edd26b26041b32,

title = "Early empiric antibiotic exposure affects gut microbiota development of very preterm infants",

abstract = "Background: After birth, antibiotics are frequently administered to preterm infants for suspected early onset sepsis (EOS). Early empiric antibiotic exposure (EEAE) may disrupt the gut microbiota of preterm infants. This study investigates the association between EEAE duration and gut microbiota dynamics in the first month of life in very preterm infants. Methods: A selected cohort of 127 very preterm infants (<30 weeks gestation) without antibiotic exposure after the first week of life, was stratified into 3 EEAE groups: non (n = 36), short (48–96 h; n = 56), and long-exposed (96–192 h; n = 35). Microbiota composition was analyzed by 16S rRNA gene amplicon sequencing of fecal samples collected at week 1–4. Results: EEAE duration was associated with increased alpha-diversity over time. Veillonella and Enterococcus were significantly lower in EEAE groups compared to non-exposed infants. Four microbial community types (CTs) were identified independent of antibiotic duration. Both EEAE groups had a higher prevalence of the Staphylococcus CT. Conclusion: Both short and long EEAE are associated with changes in the preterm gut microbiota, impacting alpha-diversity, taxonomic composition, and one community type{\textquoteright}s prevalence in the first month of life. These findings underscore the impact of antibiotic initiation for suspected EOS on the preterm gut microbiota. Impact: This multicenter cohort study investigates the impact of early empiric antibiotic exposure in very preterm infants on the gut microbiota during the first month of life. It includes a unique control group of infants without any antibiotic exposure. It shows both short and long early empiric antibiotic exposure affects the gut microbiota diversity, composition, and community type during the first month of life. Efforts aimed at reducing the initiation of early empirical antibiotic treatment in very preterm infants with suspected early-onset sepsis may help mitigate disruptions to the developing gut microbiota.",

author = "\{van Wesemael\}, \{Aranka J.\} and Kelly Klomp and Malinowska, \{Anna M.\} and \{van Kaam\}, \{Anton H.\} and \{de Meij\}, \{Tim G. J.\} and Clara Belzer and Niemarkt, \{Hendrik J.\} and \{van den Akker\}, \{Chris H. P.\} and \{de Kroon\}, \{Rimke R.\} and Frerichs, \{Nina M.\} and Oldenburger, \{Nathalie J.\} and Kouwenberg-Raets, \{Marlou M. A.\} and Hulzebos, \{Christian V.\} and Esther D'Haens and \{de Boode\}, \{Willem P.\} and Vermeulen, \{Marijn J.\} and Vijlbrief, \{Daniel C.\} and Veerle Cossey and \{Generation P study group\}",

year = "2026",

doi = "10.1038/s41390-026-04778-y",

language = "English",

journal = "Pediatric Research",

issn = "0031-3998",

publisher = "Springer",

}

van Wesemael, AJ, Klomp, K, Malinowska, AM, van Kaam, AH, de Meij, TGJ, Belzer, C, Niemarkt, HJ, van den Akker, CHP, de Kroon, RR, Frerichs, NM, Oldenburger, NJ, Kouwenberg-Raets, MMA, Hulzebos, CV, D'Haens, E, de Boode, WP, Vermeulen, MJ, Vijlbrief, DC, Cossey, V & Generation P study group 2026, 'Early empiric antibiotic exposure affects gut microbiota development of very preterm infants', Pediatric Research. https://doi.org/10.1038/s41390-026-04778-y

TY - JOUR

T1 - Early empiric antibiotic exposure affects gut microbiota development of very preterm infants

AU - van Wesemael, Aranka J.

AU - Klomp, Kelly

AU - Malinowska, Anna M.

AU - van Kaam, Anton H.

AU - de Meij, Tim G. J.

AU - Belzer, Clara

AU - Niemarkt, Hendrik J.

AU - van den Akker, Chris H. P.

AU - de Kroon, Rimke R.

AU - Frerichs, Nina M.

AU - Oldenburger, Nathalie J.

AU - Kouwenberg-Raets, Marlou M. A.

AU - Hulzebos, Christian V.

AU - D'Haens, Esther

AU - de Boode, Willem P.

AU - Vermeulen, Marijn J.

AU - Vijlbrief, Daniel C.

AU - Cossey, Veerle

AU - Generation P study group

PY - 2026

Y1 - 2026

N2 - Background: After birth, antibiotics are frequently administered to preterm infants for suspected early onset sepsis (EOS). Early empiric antibiotic exposure (EEAE) may disrupt the gut microbiota of preterm infants. This study investigates the association between EEAE duration and gut microbiota dynamics in the first month of life in very preterm infants. Methods: A selected cohort of 127 very preterm infants (<30 weeks gestation) without antibiotic exposure after the first week of life, was stratified into 3 EEAE groups: non (n = 36), short (48–96 h; n = 56), and long-exposed (96–192 h; n = 35). Microbiota composition was analyzed by 16S rRNA gene amplicon sequencing of fecal samples collected at week 1–4. Results: EEAE duration was associated with increased alpha-diversity over time. Veillonella and Enterococcus were significantly lower in EEAE groups compared to non-exposed infants. Four microbial community types (CTs) were identified independent of antibiotic duration. Both EEAE groups had a higher prevalence of the Staphylococcus CT. Conclusion: Both short and long EEAE are associated with changes in the preterm gut microbiota, impacting alpha-diversity, taxonomic composition, and one community type’s prevalence in the first month of life. These findings underscore the impact of antibiotic initiation for suspected EOS on the preterm gut microbiota. Impact: This multicenter cohort study investigates the impact of early empiric antibiotic exposure in very preterm infants on the gut microbiota during the first month of life. It includes a unique control group of infants without any antibiotic exposure. It shows both short and long early empiric antibiotic exposure affects the gut microbiota diversity, composition, and community type during the first month of life. Efforts aimed at reducing the initiation of early empirical antibiotic treatment in very preterm infants with suspected early-onset sepsis may help mitigate disruptions to the developing gut microbiota.

AB - Background: After birth, antibiotics are frequently administered to preterm infants for suspected early onset sepsis (EOS). Early empiric antibiotic exposure (EEAE) may disrupt the gut microbiota of preterm infants. This study investigates the association between EEAE duration and gut microbiota dynamics in the first month of life in very preterm infants. Methods: A selected cohort of 127 very preterm infants (<30 weeks gestation) without antibiotic exposure after the first week of life, was stratified into 3 EEAE groups: non (n = 36), short (48–96 h; n = 56), and long-exposed (96–192 h; n = 35). Microbiota composition was analyzed by 16S rRNA gene amplicon sequencing of fecal samples collected at week 1–4. Results: EEAE duration was associated with increased alpha-diversity over time. Veillonella and Enterococcus were significantly lower in EEAE groups compared to non-exposed infants. Four microbial community types (CTs) were identified independent of antibiotic duration. Both EEAE groups had a higher prevalence of the Staphylococcus CT. Conclusion: Both short and long EEAE are associated with changes in the preterm gut microbiota, impacting alpha-diversity, taxonomic composition, and one community type’s prevalence in the first month of life. These findings underscore the impact of antibiotic initiation for suspected EOS on the preterm gut microbiota. Impact: This multicenter cohort study investigates the impact of early empiric antibiotic exposure in very preterm infants on the gut microbiota during the first month of life. It includes a unique control group of infants without any antibiotic exposure. It shows both short and long early empiric antibiotic exposure affects the gut microbiota diversity, composition, and community type during the first month of life. Efforts aimed at reducing the initiation of early empirical antibiotic treatment in very preterm infants with suspected early-onset sepsis may help mitigate disruptions to the developing gut microbiota.

U2 - 10.1038/s41390-026-04778-y

DO - 10.1038/s41390-026-04778-y

M3 - Article

SN - 0031-3998

JO - Pediatric Research

JF - Pediatric Research

ER -

Early empiric antibiotic exposure affects gut microbiota development of very preterm infants

Abstract

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