The Impact of Early Life Experiences and Gut Microbiota on Neurobehavioral Development in Preterm Infants: A Longitudinal Cohort Study

Abstract

Objectives: The objective of this study is to investigate the impact of early life experiences and gut microbiota on neurobehavioral development in preterm infants during neonatal intensive care unit (NICU) hospitalization. Methods: Preterm infants were followed from 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 a high level of pain/stress during the NICU hospitalization had higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs and taxa belonging to seven genera, i.e., 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 in preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress and feeding in the NICU. The gut microbiota and acute pain/stressful experiences dynamically impact the neurobehavioral development in preterm infants during their NICU hospitalization.

Multi-Omics Analysis of Gut Microbiota and Host Transcriptomics Reveal Dysregulated Immune Response and Metabolism in Young Adults with Irritable Bowel Syndrome

“…Paired-end sequences were combined into contigs and aligned against to the SILVA 132 V4 16 S rRNA gene reference alignment database with poor-quality sequences removed. Operational taxonomic units (OTUs) were determined at a 97% identity [ 46 , 47 ]. Linear discriminant analysis (LDA) effect size (LEfSe) [ 48 ] was used to identify the significantly enriched abundant taxa between the microbiota composition of IBS subjects and HCs.…”

The Interaction between Stress and Inflammatory Bowel Disease in Pediatric and Adult Patients

“…Neurobehavioral outcomes are assessed using the NICU Network Neurobehavioral Scale (NNNS), which is a standardized score and includes, among others, stress, handling, and quality of movement [ 78 ]. It is shown that infants who had less acute stressful events during hospitalization had improved neurobehavioral outcomes [ 73 , 79 ]. Several gut bacteria were studied in terms of their link with compromised neurodevelopmental outcomes.…”

“…Chen J et al conducted a longitudinal study and identified eight gut microbiome bacterial communities associated with neurobehavioral profiles in early life. The vast amount of Enterobacteriaceae is linked to an increased NSTRESS score [ 79 ]. Another study suggested that Klebsiella overgrowth was associated with brain injury involving immunological alterations [ 75 ].…”

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 ).…”