Metagenomic signatures of early life hospitalization and antibiotic treatment in the infant gut microbiota and resistome persist long after discharge

Because hospitalized preterm infants are vulnerable to infection, they receive frequent and often prolonged exposures to antibiotics. It is not known if the short-term effects of antibiotics on the preterm infant gut microbiota and resistome persist after discharge from neonatal intensive care units. Here, we use complementary metagenomic, culture based, and machine learning techniques to interrogate the gut microbiota and resistome of antibiotic-exposed preterm infants, during and after hospitalization, and compare these readouts to antibiotic-naïve healthy infants sampled synchronously. We find a persistently enriched gastrointestinal antibiotic resistome, prolonged carriage of multidrug resistant Enterobacteriaceae, and distinct antibiotic-driven patterns of microbiota and resistome assembly in extremely preterm infants who received early life antibiotics. The collateral damage of early life antibiotic treatment and hospitalization in preterm infants is long-lasting. We urge development of strategies to reduce these consequences in highly vulnerable neonatal populations.