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

Preterm birth correlates with brain dysmaturation and neurocognitive impairment. The gut microbiome associates with behavioral outcomes in typical development, but its relationship with neurodevelopment in preterm infants is unknown. We characterize fecal microbiome in a cohort of 147 neonates enriched for very preterm birth using 16S-based and shotgun metagenomic sequencing. Delivery mode strongly correlates with the preterm microbiome shortly after birth. Low birth gestational age, infant sex assigned at birth, and antibiotics associate with microbiome composition at neonatal intensive care unit discharge. We integrate these data with term-equivalent structural and diffusion brain MRI. Bacterial community composition associates with MRI features of encephalopathy of prematurity. Particularly, abundances of Escherichia coli and Klebsiella spp. correlate with microstructural parameters in deep and cortical gray matter. Metagenome functional capacity analyses suggest that these bacteria may interact with brain microstructure via tryptophan and propionate metabolism. This study indicates that the gut microbiome associates with brain development following preterm birth.