Abstract
Interventions to mitigate long-term neurodevelopmental deficits such as memory and learning impairment in preterm infants are warranted. Manipulation of the gut microbiome affects host behaviors. In this study we determined whether early maturation of the infant microbiome is associated with neurodevelopment outcomes. Germ free mice colonized at birth with human preterm infant microbiomes from infants of advancing post menstrual age (PMA) demonstrated an increase in bacterial diversity and a shift in dominance of taxa mimicking the human preterm microbiome development pattern. These characteristics along with changes in a number of metabolites as the microbiome matured influenced associative learning and memory but not locomotor ability, anxiety-like behaviors, or social interaction in adult mice. As a regulator of learning and memory, brain glial cell-derived neurotrophic factor increased with advancing PMA and was also associated with better performance in associative learning and memory in adult mice. We conclude that maturation of the microbiome in early life of preterm infants primes adult associative memory and learning ability. Our findings suggest a critical window of early intervention to affect maturation of the preterm infant microbiome and ultimately improve neurodevelopmental outcomes.