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

Jie Chen; Hongfei Li; Tingting Zhao; Kun Chen; Ming-Hui Chen; Zhe Sun; Wanli Xu; Kendra Maas; Barry M Lester; Xiaomei S Cong

doi:10.3390/microorganisms11030814

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

Microorganisms. 2023 Mar 22;11(3):814. doi: 10.3390/microorganisms11030814.

Authors

Jie Chen^{1

2}, Hongfei Li³, Tingting Zhao^{2

4}, Kun Chen³, Ming-Hui Chen³, Zhe Sun^{3

5}, Wanli Xu², Kendra Maas⁶, Barry M Lester⁷, Xiaomei S Cong^{2

4

8}

Affiliations

¹ College of Nursing, Florida State University, Tallahassee, FL 32306, USA.
² School of Nursing, University of Connecticut, Storrs, CT 06269, USA.
³ Department of Statistics, University of Connecticut, Storrs, CT 06269, USA.
⁴ School of Nursing, Yale University, Orange, CT 06477, USA.
⁵ Department of Biostatistics, School of Public Health, Yale University, New Haven, CT 06520, USA.
⁶ Microbial Analysis, Resources, and Services (MARS), University of Connecticut, Storrs, CT 06269, USA.
⁷ Brown Center for the Study of Children at Risk, Departments of Psychiatry and Pediatrics, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
⁸ Institute for Systems Genomics, University of Connecticut, Farmington, CT 06030, USA.

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.

Keywords: NICU; feeding; gut microbiota; infants; neurobehavioral development; pain; preterm; stress.

Abstract

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