Dynamics of early gut microbiota maturation in extremely preterm infants and neurodevelopment at 2 years of age in a probiotic intervention trial.

Preterm birth is associated with a high risk of long-term neurological deficits. Although research underscores the role of the gut microbiome in the gut-brain axis, the mechanisms of neurodevelopmental impairment remain elusive. In this prospective observational study (PROPEL), we evaluated whether early gut microbiota development and Limosilactobacillus reuteri supplementation to extremely preterm infants with extremely low birth weight (EPT-ELBW) are associated with neurodevelopment at 2 years. Gut microbiota was characterized by 16S sequencing, and neurodevelopment was assessed by Bayley-III score. Microbiota composition constellations and lower microbial diversity, but not single bacteria, are associated with impaired neurodevelopment. Microbial maturation over the first month was discriminative for motor development, with higher abundance of E. coli and Enterococcus relative to Cutibacterium associated with impairment. L. reuteri supplementation did not seem to affect neurodevelopment via the gut microbiome. In conclusion, dynamics of gut microbiota maturation during early life may impact neurodevelopment in EPT-ELBW infants.