From microbes to milestones: Gut bacterial abundances and functional pathways associate with neurodevelopment following preterm birth

The early life gut microbiome has been suggested to be a potential driver of neurocognitive development. Evidence for this relationship in preterm children, who are at increased risk of both gut microbiome disruptions and neurodevelopmental impairment, is scarce. In a sample of 73 very preterm infants drawn from a prospective birth cohort, we assessed associations between the neonatal gut microbiome and neurodevelopment at 9 months and 2 years. The gut microbiome was profiled from stool samples collected prior to NICU discharge using shotgun metagenomics. By taking a consensus-based analytic approach, we found strong evidence for associations between the abundances of several gut bacterial species and measures related to autistic traits (e.g. Klebsiella spp. ), socio-emotional development, including temperament (e.g. Enterobacter cloacae complex, Veillonella parvula ), and executive functioning ( Clostridium perfringens ). The abundances of functional modules involved in gut-brain signalling, particularly those involved in histamine, tryptophan and quinolinic acid metabolism, were associated with measures related to executive functioning and cognitive-behavioural flexibility. This study provides evidence that the neonatal gut microbiome composition may affect longer-term neurodevelopmental profiles following preterm birth, particularly those related to socio-emotional development, autistic traits and executive functioning.