Pain, Gut Microbiome and Neurodevelopment in Preterm Infants

Cong, Xiaomei

Purpose: The purpose of this presentation is to discuss the state-of-the-science of recent research for the importance of the brain-gut-microbiota axis in regulation of pain/stress in early life and the use of advanced technologies of microbiome genomic sequencing in predicting pain/stress responses and neurodevelopmental outcomes in high risk preterm infants.

Methods: A prospective longitudinal study was conducted. Sixty preterm infants (26 0/7 – 32 6/7 weeks gestational age) were recruited at birth and followed-up for 3 weeks. Outcome measurements are gut microbiota (16S rRNA and metagenomic sequencing), early life pain/stress experience, and neurodevelopmental outcomes. Stool samples and pain/stress levels were measured daily and neurodevelopmental outcomes were examined at 35-36 weeks post-menstrual age prior to NICU discharge. Exploratory data analysis was conducted with a focus on the evolution in each variable’s distribution over time and linkages among variables. The associations of pain/stress, gut microbiome diveristy and abundance of specific bacteria, and neurodevelopmental outcomes were analyzed using mixed effect models.

Results: Preterm infants experienced large amount of painful/stressful event in their early life during the NICU stay. Accute and chronic pain/stressors were significant predictors for neurodevelopmental responses. Preterm infants’ gut microbiome patterns were diverse among individual infants. Pain/stressor scores account for greater than 10% of the variability seen in the microbiome community and there is an association between the gut microbiome diversity and neurodevelopmental outcomes. Indicator species analysis showed that infant who experienced less pain during NICU stay had higher abundance of Bacteroides and Lactobacillus, while infant who experienced more painful events had higher abundance of Pantoea and Aeromonadaceae (Proteobacteria phyla), which are potential pathogens in infant intestinal tract.

Conclusion: The brain-gut signaling system and the role of the gut microbiome are remarkably related to pain/sress in early life. Understanding mechanisms by which early life experience alters neurodevelopment via the brain-gut-microbiota axis will help clinicians to develop neuroprotective strategies to better predict outcomes and to provide corresponding interventions.