The impact of early life experiences and gut microbiota on neurobehavioral development among preterm infants: A longitudinal cohort study

Abstract

Objectives: To investigate the impact of early life experiences and gut microbiota on neurobehavioral development among preterm infants during neonatal intensive care unit (NICU) hospitalization. Methods: Preterm infants were followed from the NICU admission until their 28th postnatal day or until discharge. Daily stool samples, painful/stressful experiences, feeding patterns, and other clinical and demographic data were collected. Gut microbiota was profiled using 16S rRNA sequencing, and operational taxonomic units (OTUs) were selected to predict the neurobehaviors. The neurobehavioral development was assessed by the Neonatal Neurobehavioral Scale (NNNS) at 36 to 38 weeks of post-menstrual age (PMA). Fifty-five infants who had NNNS measurements were included in the sparse log-contrast regression analysis. Results: Preterm infants who experienced high level of pain/stress during the NICU hospitalization that were associated with higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with of NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs, taxa belong to seven genera including Enterobacteriaceae_unclassified, Escherichia-Shigella, Incertae_Sedis, Veillonella, Enterococcus, Clostridium_sensu_stricto_1, and Streptococcus with five belonging to Firmicutes and two belonging to Proteobacteria phylum. The enriched abundance of Enterobacteriaceae_unclassified (OTU17) and Streptococcus (OTU28) were consistently associated with less optimal neurobehavioral outcomes. The other six OTUs were also associated with infant neurobehavioral responses depending on days at NICU stay. Conclusions: This study explored the dynamic impact of specific OTUs on neurobehavioral development among preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress, and feeding in the NICU.

Examining associations among caregiver stress, social support, and the infant gut microbiota

“…Veillonella, Clostridium sensu stricto, Ruminococcus, Intestinibacter, and Blautia as well as an unspecified genus from the Lachnospiraceae family. Some of the taxa we identified, such as Veillonella and Clostridium sensu stricto, have been previously identified in studies of infant and child gut microbiota and brain and behavioral development (Acuña et al, 2021;Chen et al, 2023;Flannery et al, 2020), although the directionality of associations between taxa and child outcomes has differed between studies. Warner and colleagues (2023) identified a few species of bacteria from Veillonella that were differentially abundant in infants as a function of prenatal caregiver social wellbeing.…”

Key roles of glial cells in the encephalopathy of prematurity

“…Recent evidence suggests that the gut microbiota of preterm infants is associated with early cognitive and behavioral neurodevelopment (Chen et al, 2023; Sarkar et al, 2022) and has been identified as a potential biomarker of neurodevelopmental delay in preterm infants (Roze et al, 2020). Disruption of the maturation and development of the microbiome has also been linked to a number of fatal diseases in preterm infants, including NEC and late‐onset sepsis (Masi & Stewart, 2019; Thanert et al, 2021).…”