Intravenous Antibiotics in Preterm Infants have a Long-Term Negative Effect upon Microbiome Development Throughout Preterm Life

Intestinal dysbiosis is implicated in the origins of necrotising enterocolitis and late-onset sepsis in preterm babies. However, the effect of modulators of bacterial growth (e.g. antibiotics) upon the developing microbiome is not well-characterised. Using high-throughput 16S rRNA gene sequencing combined with contemporaneous clinical data collection, the within-subject relationship between antibiotic administration and microbiome development was assessed, in comparison to preterm infants with minimal antibiotic exposure. During courses of antibiotics, diversity progression fell in comparison to that seen outside periods of antibiotic use (-0.71units/week vs. +0.63units/week, p<0.01); Enterobacteriaceae relative abundance progression conversely rose (+10.6%/week vs. -8.9%/week, p<0.01). After antibiotic cessation, diversity progression remained suppressed (+0.2units/week, p=0.02). Antibiotic use has an acute and longer-lasting impact on the developing preterm intestinal microbiome. This has clinical implications with regard to the contribution of antibiotic use to evolving dysbiosis, and affects the interpretation of existing microbiome studies where this effect modulator is rarely accounted for.