Dynamics of early gut microbiota maturation in extremely preterm infants in relation with neurodevelopment at 2 years

Preterm birth yields survivors with heightened susceptibility to long-term neurological deficits, with severity being linked to gestational age. The mechanisms behind neurodevelopmental impairment remain elusive, although research underscores the role of the gut microbiome in regulating the gut-brain axis. In this prospective observational cohort study (PROPEL-study follow-up) we evaluated whether modulation of the gut microbiota by Limosilactobacillus reuteri supplementation to 105 extremely preterm infants with extremely low birth weight (EPT-ELBW), as well as their microbiota development during the first month of life, are associated with neurodevelopment at two years of age. The gut microbiota was characterized with 16S amplicon sequencing, and neurodevelopment was assessed with clinical examination and the Bayley-III score. Our results indicate that specific microbiota composition constellations are associated with impaired neurodevelopment, as indicated by alpha- and beta-diversity being discriminative for neurodevelopment, but not a single bacterium, with increased bacterial diversity being associated to normal neurodevelopment. Microbial maturation over the first month of life was also discriminative for neurodevelopment, where higher abundance of E. coli and Enterococcus in relation to Enterobacter was associated to impaired neurodevelopment. In conclusion, the dynamics of gut microbiota maturation during early of life may have an impact on neurodevelopment in EPT-ELBW infants.