The neonatal gut microbiota: a role in the encephalopathy of prematurity

Summary Preterm birth associates with atypical brain development and neurocognitive impairment. The gut microbiome is implicated in neurobehavioural outcomes of typically developing infants and children, but its relationship with neurodevelopment in preterm infants is unknown. We characterised the faecal microbiome in a cohort of 147 neonates enriched for very preterm birth (<32 weeks’ gestation) using 16S-based and shotgun metagenomic sequencing. Delivery mode had the strongest association with preterm microbiome shortly after birth; low birth gestational age, infant sex and antibiotics significantly associated with microbiome composition at NICU discharge. Thereafter, we integrated these data with term-equivalent structural and diffusion brain MRI. Bacterial community composition associated with MRI features of encephalopathy of prematurity. Particularly, abundances of Escherichia coli and Klebsiella spp. correlated with microstructural parameters in deep and cortical grey matter. Metagenome functional capacity analyses suggested that these bacteria may interact with brain microstructural development via tryptophan and propionate metabolism. This study indicates that gut microbiome associates with brain development following preterm birth.