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Early antibiotic exposure and vaccine immune responses in preterm infants: potential sex-specific differences

Laura Haag1, Stefanie Dietz-Ziegler1,2, Julian Schwarz1

  • 1Department of Neonatology, Tuebingen University Children's Hospital, Tuebingen, Germany.

Gut Microbes
|June 27, 2026
PubMed

Insights

Early antibiotic exposure in preterm infants can impair vaccine responses, particularly in girls. This may be linked to microbiome and immune cell changes, affecting immune development.

Area of Science:

  • Neonatal immunology
  • Microbiome research
  • Vaccinology

Background:

  • Neonatal sepsis is a significant risk for preterm infants, often leading to early antibiotic use.
  • The effects of early antibiotics on preterm immune development are not well understood, unlike in term-born neonates.

Purpose of the Study:

  • To investigate how early antibiotic exposure impacts vaccine antibody titers at four months corrected age in preterm infants.
  • To explore potential sex-specific differences in these effects.

Main Methods:

  • Prospective observational study of 69 preterm infants (<32 weeks gestational age).
  • Analysis of vaccine titers (Bordetella pertussis, Haemophilus influenzae), immune cell profiles, gut microbiome composition, and metabolomics at postnatal day 14 and 4 months corrected age.
  • Comparison between infants with and without early antibiotic exposure.

Main Results:

  • Antibiotic-exposed preterm infants had reduced vaccine antibody titers, with a more pronounced effect in girls.
  • Antibiotic-exposed girls showed increased monocytes and myeloid-derived suppressor cells (MDSCs), inversely correlating with antibody titers.
  • Early antibiotics altered gut microbiome composition and led to distinct metabolomic profiles in girls, linked to immune cell changes.

Conclusions:

  • Early antibiotic exposure negatively affects vaccine responses in preterm infants, with potential sex-specific susceptibility.
  • Antibiotic-induced alterations in the microbiome and metabolome may promote immune-suppressive cell populations, potentially weakening adaptive immunity to vaccines.

Keywords:
Antibioticsmicrobiomepreterm infantssex-differencesvaccination

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