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

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. 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. 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. 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. 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.