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

Abstract

AbstractPreterm birth is associated with atypical brain development and alterations in the gut microbiome. Variation in gut microbiome composition associates with neurobehavioural outcomes, but its relationship with brain development in preterm infants is unknown. First, we characterised the faecal microbiome in an observational cohort of 135 preterm (<32 weeks’ gestation) and 12 term neonates using 16S-based and shotgun metagenomic sequencing. Apart from sampling age, 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. Second, we integrated these data with structural and diffusion MRI at term-equivalent age. Bacterial community composition associated with MRI features of encephalopathy of prematurity. Particularly, abundances ofEscherichia coliandKlebsiellaspp. correlated with microstructural parameters in deep and cortical grey matter. Metagenome functional capacity analyses using gut-brain modules suggested that these bacteria interact with brain microstructural development via tryptophan and propionate metabolism. This study indicates a role for microbiota-brain interactions in brain development following preterm birth.