Antibiotic exposure prevents acquisition of beneficial metabolic functions in the preterm infant gut microbiome

Background: Aberrations in the preterm microbiome following antibiotic therapy have been reported in previous studies. The objective of this study was to probe potential underlying mechanisms between this observation and susceptibility to adverse prematurity-related outcomes. Results: Metagenomic shotgun sequencing was performed on 133 stool and 253 skin samples collected at 1 and 3 weeks of age from 68 infants born at <36 weeks postmenstrual age and birth weight <2000 g. After accounting for gestational age and maternal antibiotics, the distribution of organisms in all samples and the corresponding metabolic pathway abundance were compared between infants exposed to postnatal antibiotics and antibiotics-naive infants. In antibiotic-naive infants, gestational and postnatal age imparted similar trajectories on maturation of the microbial community and associated metabolic functional capacity, with postnatal age exerting greater contribution. Antibiotic exposure was associated with reversal in maturation trajectory from the first week to the third week of age (p< 0.001). Butyrate-producing genera, including Clostridium and Blautia, were significantly more abundant in antibiotic-naive neonates at 3 weeks postnatal age. Correspondingly, metabolic pathways required for short-chain fatty acid synthesis were significantly increased in antibiotic-naive infants, but not in antibiotic-exposed neonates, at 3 weeks after birth. Conclusions: Early brief antibiotic exposure markedly disrupts developmental trajectory of the neonatal microbiome and its corresponding functional capacity. Our findings may provide a mechanistic explanation for the known associations between antibiotic use and adverse outcomes in preterm infants.

Automated summary

This study found that early brief exposure to antibiotics significantly disrupts the developmental trajectory of the neonatal microbiome, leading to a corresponding impairment in its metabolic functional capacity. Infants not exposed to antibiotics had higher abundance of butyrate-producing genera and increased metabolic pathways for short-chain fatty acid synthesis at 3 weeks postnatally.