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

چکیده اصلی

Neonatal sepsis represents a major risk in preterm infant care, resulting in widespread early-life antibiotic exposure. While the latter has been linked to immune maturation in term-born neonates, its impact on preterm immune development remains unclear. The aim of this prospective observational study was to investigate the effect of early antibiotic exposure on vaccine titers at a corrected age of four months. To achieve this, blood and stool samples were analyzed from 69 preterm infants (<32 weeks gestational age; 35 with 34 without antibiotic exposure during the first postnatal week) at postnatal day 14 and again at four months corrected age. We assessed vaccine-induced antibody titers against Bordetella pertussis and Haemophilus influenzae, immune cell profiles (flow cytometry), gut microbiome composition (16S rRNA sequencing), and plasma amino acid and acylcarnitine levels (tandem mass spectrometry). Preterm infants exposed to early antibiotics showed reduced antibody titers following vaccination, with differences appearing more pronounced in girls. Antibiotic-exposed girls displayed increased monocytes and myeloid-derived suppressor cells (MDSCs), both of which inversely correlated with antibody titers. Early antibiotic exposure was associated with differences in microbial community types at postnatal day 14, with Klebsiella-dominated and Bifidobacteria-lacking communities occurring more frequently in antibiotic-exposed infants. Antibiotic-exposed girls exhibited distinct metabolomic alterations, including elevated levels of two unsaturated fatty acids that negatively correlated with monocyte and MDSC abundance. Our findings suggest that early antibiotic exposure impairs vaccine responses in preterm infants and indicates a potentially sex-specific susceptibility. Antibiotic-driven changes in the microbiome and metabolome may sustain suppressive innate immune cell populations, which may in turn weaken adaptive responses to vaccination.

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